ANTIMICROBIAL AGENTS

Abstract

The present invention relates to antimicrobial agents against Gram-positive bacteria, in particular to fusion proteins composed of an enzyme having the activity of degrading the cell wall of Gram-positive bacteria and an additional peptide stretch fused to the enzyme at the N- or C-terminus. Moreover, the present invention relates to nucleic acid molecules encoding said fusion protein, vectors comprising said nucleic acid molecules and host cells comprising either said nucleic acid molecules or said vectors. In addition, the present invention relates to said fusion protein for use as a medicament, in particular for the treatment or prevention of Gram-positive bacterial infections, as diagnostic means or as cosmetic substance. The present invention also relates to the treatment or prevention of Gram-positive bacterial contamination of foodstuff, of food processing equipment, of food processing plants, of surfaces coming into contact with foodstuff, of medical devices, of surfaces in hospitals and surgeries. Further, the present invention relates to a pharmaceutical composition comprising said fusion protein.

Description

[0001] The present invention relates to antimicrobial agents against Gram-positive bacteria, in particular to fusion proteins composed of an enzyme having the activity of degrading the cell wall of Gram-positive bacteria and an additional peptide stretch fused to the enzyme at the N- or C-terminus. Moreover, the present invention relates to nucleic acid molecules encoding said fusion protein, vectors comprising said nucleic acid molecules and host cells comprising either said nucleic acid molecules or said vectors. In addition, the present invention relates to said fusion protein for use as a medicament, in particular for the treatment or prevention of Gram-positive bacterial infections, as diagnostic means or as cosmetic substance. The present invention also relates to the treatment or prevention of Gram-positive bacterial contamination of foodstuff, of food processing equipment, of food processing plants, of surfaces coming into contact with foodstuff, of medical devices, of surfaces in hospitals and surgeries. Further, the present invention relates to a pharmaceutical composition comprising said fusion protein.

[0002] In contrast to Gram-negative bacteria, Gram-positive bacteria do not possess an outer membrane. The cytoplasmic membrane is surrounded by an up to 25 nm thick layer of peptidoglycan (which is only up to 5 nm for Gram-negative bacteria) which forms the cell wall. Main purpose of the cell wall of Gram-positives is to maintain bacterial shape and to counteract the internal bacterial cell pressure. Peptidoglycan, or murein, is a polymer consisting of sugars and amino acids. The sugar component consists of alternating residues of β-(1,4) linked N-acetylglucosamine and N-acetylmuramic acid residues compose the sugar components. A peptide chain of three to five amino acids is attached to the N-acetylmuramic acid. The peptide chain can be cross-linked to the peptide chain of another strand forming a 3D mesh-like layer. The peptide chain may contain D- and L-amino acid residues and the composition may vary for different bacteria.

[0003] A special situation is found in case of Mycobacteria which are usually considered Gram-positive. Mycobacteria were recently shown to posses an outer cell membrane. All Mycobacteria share a characteristic thick cell wall, which is hydrophobic, waxy, and rich in mycolic acids/mycolates. The cell wall consists of the hydrophobic mycolate layer and a peptidoglycan layer held together by arabinogalactan, a polysaccharide. To overcome the thick cell wall of Mycobacteria a combined action of the new antimicrobial agents with a chitinase or a similar protein to disrupt the polysaccharide layer may be necessary.

[0004] Various types of agents having bactericidal or bacteriostatic activity are known, e.g. antibiotics, endolysins, antimicrobial peptides and defensins. Increasing microbial resistance to antibiotics, however, is creating difficulties in treating more and more infections caused by bacteria. Particular difficulties arise with infections caused by Gram-positive bacteria like Staphylococcus aureus, Enterococci, Streptococci, Listeria monocytogenes and Clostridium difficile, especially with e.g. Methicillin-resistant Staphylococcus aureus and Vancomycin-resistant Enterococci.

[0005] Endolysins are peptidoglycan hydrolases encoded by bacteriophages (or bacterial viruses). They are synthesized during late gene expression in the lytic cycle of phage multiplication and mediate the release of progeny virions from infected cells through degradation of the bacterial peptidoglycan. They are either β(1,4)-glycosylases (lysozymes), transglycosylases, amidases or endopeptidases. Antimicrobial application of endolysins was already suggested in 1991 by Gasson (GB2243611). Although the killing capacity of endolysins has been known for a long time, the use of these enzymes as antibacterials was ignored due to the success and dominance of antibiotics. Only after the appearance of multiple antibiotic resistant bacteria this simple concept of combating human pathogens with endolysins received interest. A compelling need to develop totally new classes of antibacterial agents emerged and endolysins used as `enzybiotics`--a hybrid term of `enzymes` and `antibiotics`--perfectly met this need. In 2001, Fischetti and coworkers demonstrated for the first time the therapeutic potential of bacteriophage C1 endolysin towards group A streptococci (Nelson et al., 2001). Since then many publications have established endolysins as an attractive and complementary alternative to control bacterial infections, particularly by Gram-positive bacteria. Subsequently different endolysins against other Gram-positive pathogens such as Streptococcus pneumoniae (Loeffler et al., 2001), Bacillus anthracis (Schuch et al., 2002), S. agalactiae (Cheng et al., 2005) and Staphylococcus aureus (Rashel et al, 2007) have proven their efficacy as enzybiotics. However, it is also known that endolysins can, under some conditions (e.g. high ionic strength), create stable protoplast, where the internal bacterial cell pressure is not sufficient to lead to a cell burst. Under these conditions the bacterial cell wall can regenerate and the bacteria will survive.

[0006] Antimicrobial peptides (AMPs) represent a wide range of short, cationic or amphipatic gene-encoded peptide antibiotics that can be found in virtually every organism. Different AMPs display different properties, and many peptides in this class are being intensively researched not only as antibiotics, but also as templates for cell-penetrating peptides. Despite sharing a few common features (e.g., cationicity, amphipathicity and short size), AMP sequences vary greatly, and at least four structural groups (α-helical, β-sheet, extended and looped) have been proposed to accommodate the diversity of the observed AMP conformations. Likewise, several modes of action as antibiotics have been proposed, and it was shown e.g. that the primary target of many of these peptides is the cell membrane whereas for other peptides the primary target is cytoplasmic invasion and disruption of core metabolic functions. AMPs may become concentrated enough to exhibit cooperative activity despite the absence of specific target binding; for example, by forming a pore in the membrane, as is the case for most AMPs. However, this phenomenon has only been observed in model phospholipid bilayers, and in some cases, AMP concentrations in the membrane that were as high as one peptide molecule per six phospholipid molecules were required for these events to occur. These concentrations are close to, if not at, full membrane saturation. As the minimum inhibitory concentration (MIC) for AMPs is typically in the low micromolar range, scepticism has understandably arisen regarding the relevance of these thresholds and their importance in vivo (Melo et al., Nature reviews, Microbiology, 2009, 245).

[0007] Defensins are a large family of small, cationic, cysteine- and arginine-rich antimicrobial peptides, found in both vertebrates and invertebrates. Defensins are divided into five groups according to the spacing pattern of cysteines: plant, invertebrate, β-, β-, and θ-defensins. The latter three are mostly found in mammals. α-defensins are proteins found in neutrophils and intestinal epithelia. β-defensins are the most widely distributed and are secreted by leukocytes and epithelial cells of many kinds. θ-defensins have been rarely found so far e.g. in leukocytes of rhesus macaques. Defensins are active against bacteria, fungi and many enveloped and nonenveloped viruses. However, the concentrations needed for efficient killing of bacteria are mostly high, i.e. in the α-molar range. Activity of many peptides may be limited in presence of physiological salt conditions, divalent cations and serum. Depending on the content of hydrophobic amino acid residues Defensins also show haemolytic activity.

[0008] Thus, there is a need for new antimicrobial agents against Gram-positive bacteria.

[0009] This object is solved by the subject matter defined in the claims.

[0010] The term "protein" as used herein refers synonymously to the term "polypeptide". The term "protein" as used herein refers to a linear polymer of amino acid residues linked by peptide bonds in a specific sequence. The amino-acid residues of a protein may be modified by e.g. covalent attachments of various groups such as carbohydrates and phosphate. Other substances may be more loosely associated with the polypeptide chains, such as heme or lipid, giving rise to the conjugated proteins which are also comprised by the term "protein" as used herein. The various ways in which the polypeptide chains fold have been elucidated, in particular with regard to the presence of alpha helices and beta-pleated sheets. The term "protein" as used herein refers to all four classes of proteins being all-alpha, all-beta, alpha/beta and alpha plus beta. Moreover, the term "protein" refers to a complex, wherein the complex refers to a homomer.

[0011] The term "fusion protein" as used herein refers to an expression product resulting from the fusion of two nucleic acid sequences. Such a protein may be produced, e.g., in recombinant DNA expression systems. Moreover, the term "fusion protein" as used herein refers to a fusion of a first amino acid sequence as e.g. an enzyme, with a second or further amino acid sequence. The second or further amino acid sequence may define a domain or any kind of peptide stretch. Preferably, said second and/or further amino acid sequence is foreign to and not substantially homologous with any domain of the first amino acid sequence.

[0012] The term "peptide stretch" as used herein refers to any kind of peptide linked to a protein such as an enzyme.

[0013] The term "peptide" as used herein refers to short polypeptides consisting of from about 2 to about 100 amino acid residues, more preferably from about 4 to about 50 amino acid residues, more preferably to about 5 to 30 amino acid residues, wherein the amino group of one amino acid residue is linked to the carboxyl group of another amino acid residue by a peptide bond. A peptide may have a specific function. A peptide can be a naturally occurring peptide or a synthetically designed and produced peptide. The peptide can be, for example, derived or removed from a native protein by enzymatic or chemical cleavage, or can be prepared using conventional peptide synthesis techniques (e.g., solid phase synthesis) or molecular biology techniques (see Sambrook, J. et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press, Cold Spring Harbor, N.Y. (1989)). Examples of naturally occurring peptides are antimicrobial peptides, defensins, sushi peptides. Examples of synthetically produced peptides are polycationic, amphiphatic or hydrophobic peptides. A peptide in the meaning of the present invention does not refer to His-tags, Strep-tags, thioredoxin or maltose binding proteins (MBP) or the like, which are used to purify or locate proteins.

[0014] The term "endolysin" as used herein refers to an enzyme which is suitable to hydrolyse bacterial cell walls. "Endolysins" comprise of at least one "enzymatically active domain" (EAD) having at least one of the following activities: endopeptidase, chitinase, T4 like muraminidase, lambda like muraminidase, N-acetyl-muramoyl-L-alanine-amidase (amidase), muramoyl-L-alanine-amidase, muramidase, lytic transglycosylase (C), lytic transglycosylase (M), N-acetyl-muramidase, N-acetyl-glucosaminidase (lysozyme) or transglycosylases as e.g. KZ144 and EL188. In addition, the endolysins may contain also regions which are enzymatically inactive, and bind to the cell wall of the host bacteria, the so-called CBDs (cell wall binding domains).

[0015] The term "CBD" as used herein refers to the cell wall binding domain of an endolysin. In endolysins being specific for Gram-positive bacteria the CBD is often found at the C-terminus, but may also be found N-terminal or somewhere else within the protein. Often CBD domains mediate binding of the endolysin to the bacterial cell wall but have no enzymatic activity in terms of hydrolyzing the cell wall.

[0016] The term "EAD" as used herein refers to the enzymatically active domain of an endolysin. The EAD is responsible for hydrolysing bacterial peptidoglycans. It exhibits at least one enzymatic activity of an endolysin. The EAD can also be composed of more than one enzymatically active module.

[0017] The term "autolysins" refers to enzymes related to endolysins but encoded by bacteria and involved in e.g. cell division. An overview of autolysins is can be found in "Bacterial peptidoglycan (murein) hydrolases. Vollmer W, Joris B, Charlier P, Foster S. FEMS Microbiol Rev. 2008 March; 32(2):259-86".

[0018] The term "bacteriocin" as used herein refers to protein-like, polypeptide-like or peptide-like substances which are able to inhibit the growth of other bacteria. Some bacteriocins are capable of degrading bacterial cell walls like Lysostaphin (degrading Staphylococcus cell walls), Mutanolysin (degrading Streptococcus cell walls) and Enterolysin (degrading Enterococcus cell walls). Preferably said inhibition is specifically by means of absorption of said other bacteria to specific receptors of the bacteriocin. In general, bacteriocins are produced by microorganisms. However, the term "bacteriocin" as used herein refers both to an isolated form produced by a microorganism or to a synthetically produced form, and refers also to variants which substantially retain the activities of their parent bacteriocins, but whose sequences have been altered by insertion or deletion of one or more amino acid residues.

[0019] The term, "antimicrobial peptide" (AMP) as used herein refers to any peptide that has microbicidal and/or microbistatic activity. Thus, the term "antimicrobial peptide" as used herein refers in particular to any peptide having anti-bacterial, anti-fungal, anti-mycotic, anti-parasitic, anti-protozoal, anti-viral, anti-infectious, anti-infective and/or germicidal, algicidal, amoebicidal, microbicidal, bactericidal, fungicidal, parasiticidal, protozoacidal, protozoicidal properties.

[0020] The term "defensin" as used herein refers to a peptide present within animals, preferably mammals, more preferably humans, wherein the defensin plays a role in the innate host defense system as the destruction of foreign substances such as infectious bacteria and/or infectious viruses and/or fungi. A defensin is non-antibody microbicidal and/or tumoricidal protein, peptide or polypeptide. Examples for "defensins" are "mammalian defensins," alpha-defensins, beta-defensins, indolicidin and magainins. The term "defensins" as used herein refers both to an isolated form from animal cells or to a synthetically produced form, and refers also to variants which substantially retain the cytotoxic activities of their parent proteins, but whose sequences have been altered by insertion or deletion of one or more amino acid residues.

[0021] The term "sushi peptide" as used herein refers to complement control proteins (CCP) having short consensus repeats. The sushi module of sushi peptides functions as a protein-protein interaction domain in many different proteins. Peptides containing a Sushi domain have been shown to have antimicrobial activities.

[0022] As used herein, the term "cationic peptide" refers to a peptide having positively charged amino acid residues. Preferably a cationic peptide has a pKa-value of 9.0 or greater. Typically, at least four of the amino acid residues of the cationic peptide can be positively charged, for example, lysine or arginine. "Positively charged" refers to the side chains of the amino acid residues which have a net positive charge at about physiological conditions.

[0023] Examples of naturally occurring cationic peptides which can be recombinantly produced are defensins, magainins, melittin, and cecropins.

[0024] The term "polycationic peptide" as used herein refers to a synthetically produced peptide composed of mostly lysine and/or arginine residues.

[0025] The term "amphipathic peptide" as used herein refers to peptides having both hydrophilic and hydrophobic functional groups. Preferably, the term "amphipathic peptide" as used herein refers to a peptide having a defined arrangement of hydrophilic and hydrophobic groups e.g. amphipatic peptides may be e.g. alpha helical, having predominantly non polar side chains along one side of the helix and polar residues along the remainder of its surface.

[0026] The term "hydrophobic group" as used herein refers to chemical groups such as amino acid side chains which are substantially water insoluble, but soluble in an oil phase, with the solubility in the oil phase being higher than that in water or in an aqueous phase. In water, amino acids having a hydrophobic side chain interact with one another to generate a nonaqueous environment. Examples of amino acids with hydrophobic side chains are alanine, valine, leucine, isoleucine, phenylalanine, histidine, tryptophane and tyrosine.

[0027] The term "deletion" as used herein refers to the removal of 1, 2, 3, 4, 5 or more amino acid residues from the respective starting sequence.

[0028] The term "insertion" or "addition" as used herein refers to the insertion or addition of 1, 2, 3, 4, 5 or more amino acid residues to the respective starting sequence.

[0029] The term "substitution" as used herein refers to the exchange of an amino acid residue located at a certain position for a different one.

[0030] The present invention relates to new antibacterial agents against Gram-positive bacteria, in particular to fusion proteins composed of an enzyme having the activity of degrading the cell wall of Gram-positive bacteria and an additional peptide stretch fused to the enzyme at the N- or C-terminus or at both termini.

[0031] The fusion proteins according to the present invention have the advantage that they may prevent the regeneration of stable protoplasts and thus, preventing the survival of the bacteria which should be eliminated. The regeneration of the protoplast by the bacteria occurs under some conditions (e.g. high ionic strength), where the internal bacterial cell pressure is not sufficient to lead to a cell burst and leads to the survival of the bacteria.

[0032] In one aspect of the present invention the enzyme having the activity of degrading the cell wall of Gram-positive bacteria is an endolysine, autolysine and/or bacteriocin.

[0033] In another aspect of the present invention the enzyme may contain also regions which are enzymatically inactive, and bind to the cell wall of the host bacteria, the so-called CBDs (cell wall binding domains).

[0034] Preferred fusion proteins according to the present invention are depicted in SEQ ID NO:63 to 90. The fusion proteins according to SEQ ID NO:63 to 90 may comprise one or more additional amino acid residues on the N-terminus. Preferably the additional amino acid residue is methionine.

[0035] Preferably, the endolysin is encoded by bacteriophages specific for Gram-positive bacteria such as Gram-positive bacteria of bacterial groups, families, genera or species comprising strains pathogenic for humans or animals as listed in the following table.

TABLE-US-00001 TABLE 1 I. Phylum Actinobacteria Class: Actinobacteridae Order Actinomycetales Families: Actinomycineae: Actinomycetaceae (Actinomyces, Mobiluncus) Corynebacterineae: Mycobacteriaceae (Mycobacterium), Nocardiaceae, Corynebacteriaceae Frankineae: Frankiaceae Micrococcineae: Brevibacteriaceae Propionibacteriaceae (Propionibacterium) Order: Bifidobacteriales Families: Bifidobacteriaceae (Bifidobacterium, Falcivibrio, Gardnerella) Other subclasses: Acidimicrobidae, Coriobacteridae, Rubrobacteridae, Sphaerobacteridae II. Phylum Firmicutes Class: Bacilli Order: Bacillales: Families: Bacillaceae (Bacillus), Listeriaceae (Listeria), Staphylococcaceae (Staphylococcus, Gemella, Jeotgalicoccus) Order: Lactobacillales: Families: Enterococcaceae (Enterococcus), Lactobacillaceae (Lactobacillus, Pediococcus), Leuconostocaceae (Leuconostoc), Streptococcaceae (Lactococcus, Streptococcus) Class: Clostridia Order: Clostridiales (Clostridium, Peptostreptococcus, Selenomonas) Order: Halanaerobiales Order: Thermoanaerobacterales Class: Tenericutes/Mollicutes Order: Mycoplasmatales (Mycoplasma, Ureaplasma) Order: Entomoplasmatales (Spiroplasma) Order: Anaeroplasmatales (Erysipelothrix) Order: Acholeplasmatales (Acholeplasma) Order: Haloplasmatales (Haloplasma)

[0036] Preferably, the autolysin is encoded by Gram-positive bacteria such as Gram-positive bacteria of bacterial groups, families, genera or species comprising strains pathogenic for humans or animals as listed in table 1.

[0037] Preferably, the bacteriocin is encoded by Gram-positive bacteria such as Gram-positive bacteria of bacterial groups, families, genera or species comprising strains pathogenic for humans or animals as listed in table 1.

[0038] The enzyme according to the present invention has cell wall degrading activity against Gram-positive bacteria of bacterial groups, families, genera or species comprising strains pathogenic for humans or animals like Listeria monocytogenes, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus mutans, Streptococcus equi, Clostridium difficile, Clostridium botulinum, Clostridium tetani, Clostridium perfringens, Bacillus anthracis, Bacillus cereus, Propionibacterium acnes, Mycobacterium avium, Mycobacterium tuberculosis, Corynebacterium diphteriae, Mycoplasma pneumoniae, Actinomyces.

[0039] Preferred endolysins are Listeria phage endolysins PlyA118, PlyA500, PlyPSA, PlyA511, PlyP35, PlyP40, Staph phage Phi 11, Phi MR11, LysK, Clostridium perfringens PlyS6, Ply3626, Clostridium difficile: CD27L endolysin, Streptococcus: B30 endolysin, phage Dp-1 Pa1 amidase, C1 endolysin, Cpl-1 endolysin, PlyGBS, Enterococccus: PlyV12, Bacillus anthracis: Phage gamma endolysin PlyG.

[0040] Preferred autolysins are described in: Bacterial peptidoglycan (murein) hydrolases. Vollmer W, Joris B, Charlier P, Foster S. FEMS Microbiol Rev. 2008 March; 32(2):259-86. Epub 2008 February 11. Review. An example of a preferred autolysin is the At1A Autolysine.

[0041] Preferred bacteriocines are Lysostaphin (degrading Staphylococcus cell walls), Mutanolysin (degrading Streptococcus cell walls) and Enterolysin (degrading Enterococcus cell walls).

[0042] More preferably, the endolysin part is selected from the group consisting of Cpl-1 according to SEQ ID NO:57, Ply511 according to SEQ ID NO:58, LysK according to SEQ ID NO:59, Lysostaphin according to SEQ ID NO:60 and PA6-gp20 according to SEQ ID NO:61.

[0043] In another preferred embodiment of the present invention the endolysins, autolysins and bacteriocins of the fusion protein according to the present invention comprise modifications and/or alterations of the amino acid sequences. Such alterations and/or modifications may comprise mutations such as deletions, insertions and additions, substitutions or combinations thereof and/or chemical changes of the amino acid residues, e.g. biotinylation, acetylation, pegylation, chemical changes of the amino-, SH- or carboxyl-groups. Said endolysins, autolysins and bacteriocins of the fusion protein according to the present invention exhibit the lytic activity of the respective wild-type endolysin. However, said activity can be the same, higher or lower as the activity of the respective wild-type endolysin. Said activity can be about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190 or about 200% of the activity of the respective wild-type endolysin or even more. The activity can be measured by assays well known in the art by a person skilled in the art as e.g. the plate lysis assay or the liquid lysis assay which are e.g. described in Briers et al., J. Biochem. Biophys Methods 70: 531-533, (2007) or Donovan D M, Lardeo M, Foster-Frey J. FEMS Microbiol Lett. 2006 December; 265(1) or similar publications.

[0044] Preferably, the peptide stretch of the fusion protein according to the invention is fused to the N-terminus and/or to the C-terminus of the endolysin. In a particular preferred embodiment said peptide stretch is only fused to the N-terminus of the enzyme. In another preferred embodiment the peptide stretch is only fused to the C-Terminus of the enzyme. However, also preferred are modified fusion proteins having a peptide stretch both on the N-terminus and on the C-terminus. Said peptide stretches on the N-terminus and on the C-terminus can be the same or distinct peptide stretches. The peptide stretch can be linked to the enzyme by additional amino acid residues e.g. due to cloning reasons. Preferably, said peptide stretch can be linked to the fusion protein by at least 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 additional amino acid residues. In a preferred embodiment the peptide stretch is linked to the enzyme by the additional amino acid residues glycine and/or serine (Gly-Ser). Moreover, the peptide stretch of the fusion protein according to the invention further comprises additional amino acids on its N-terminus. Preferably, the peptide stretch comprises the amino acid methionine (Met) or alanine, methionine and glycine (Ala-Met-Gly).

[0045] The peptide stretch of the fusion protein according to the present invention is preferably covalently bound to the enzyme. Preferably, said peptide stretch consists of at least 5, more preferably at least of 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or at least 100 amino acid residues. Especially preferred is a peptide stretch comprising about 5 to about 100 amino acid residues, about 5 to about 50 or about 5 to about 30 amino acid residues. More preferred is a peptide stretch comprising about 6 to about 42 amino acid residues, about 6 to about 39 amino acid residues, about 6 to about 38 amino acid residues, about 6 to about 31 amino acid residues, about 6 to about 25 amino acid residues, about 6 to about 24 amino acid residues, about 6 to about 22 amino acid residues, about 6 to about 21 amino acid residues, about 6 to about 20 amino acid residues, about 6 to about 19 amino acid residues, about 6 to about 16 amino acid residues, about 6 to about 14 amino acid residues, about 6 to about 12 amino acid residues, about 6 to about 10 amino acid residues or about 6 to about 9 amino acid residues.

[0046] Preferably, the peptide stretch is no tag such as a His₆-tag, Strep-tag, Avi-tag, Myc-tag, Gst-tag, JS-tag, cystein-tag, FLAG-tag or other tags known in the art and no thioredoxin or maltose binding proteins (MBP). However, the peptide stretch and/or the endolysin, autolysin or bacteriocin according to the present invention may comprise in addition such tag or tags.

[0047] More preferably the peptide stretch has the function to facilitate the burst of the bacterial cell via interaction of the fusion protein with: first the peptidoglycan layer, degrading the peptidoglycan and second the cytoplasmic membrane, destabilizing the cytoplasmic membrane.

[0048] In one aspect of the present invention the fused peptide stretch is a cationic peptide, more preferably a polycationic peptide. Preferably the cationic peptide comprises one or more of the positively charged amino acid residues of lysine, arginine and/or histidine. Preferably, more than about 60, 65, 70, 75, 80, 85, 90, 95 or about 100%, of the amino acid residues in said peptide are positively charged amino acid residues. Advantageously, the cationic peptide is fused at the N-terminal and/or the C-terminal end of the enzyme having cell wall degrading activity, thus enhancing the cationicity of the fusion proteins and/or antimicrobial agents of the present invention. In another embodiment of the invention, the cationic peptide fused to the enzyme consists of at least 5, more preferably of at least 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 amino acid residues. Preferably at least about 60, 65, 70, 75, 80, 85, 90, 95 or about 100%, of the amino acid residues of the cationic peptide are either arginine or lysine. In another embodiment of the present invention the cationic peptide comprises about 3 to about 50, more preferably about 5 to about 20, for instance about 5 to about 15 amino acid residues and the said amino acid residues are either arginine or lysine residues. Preferred cationic peptides are depicted in SEQ ID NOs:13 and 14.

[0049] Especially preferred are cationic and/or polycationic peptide stretches comprising at least one motive according to SEQ ID NO: 62 (KRKKRK). In particular cationic peptide stretches comprising at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17 motives according to SEQ ID NO: 62 (KRKKRK) are preferred. More preferred are cationic peptide stretches comprising at least one KRK motive (lys-arg-lys), preferable at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 or 33 KRK motives.

[0050] In another preferred embodiment of the present invention the cationic peptide stretch comprises beside the positively charged amino acid residues, in particular lysine and/or arginine residues, neutrally charged amino acid residues, in particular glycine and/or serine residues. Preferred are cationic peptide stretches consisting of about 70% to about 100%, or about 80% to about 95%, or about 85% to about 90% positively charged amino acid residues, in particular lysine, arginine and/or histidine residues, more preferably lysine and/or arginine residues and of about 0% to about 30%, or about 5% to about 20%, or about 10% to about 20% neutrally charged amino acid residues, in particular glycine and/or serine residues. Preferred are polypeptide stretches consisting of about 4% to about 8% serine residues, of about 33% to about 36% arginine residues and of about 56% to about 63% lysine residues. Especially preferred are polypeptide stretches comprising at least one motive according to SEQ ID NO: 45 (KRXKR), wherein X is any other amino acid than lysine, arginine and histidine. Especially preferred are polypeptide stretches comprising at least one motive according to SEQ ID NO: 46 (KRSKR). More preferred are cationic stretches comprising at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or about 20 motives according to SEQ ID NO: 45 (KRXKR) or SEQ ID NO: 46 (KRSKR).

[0051] Also preferred are polypeptide stretches consisting of about 9 to about 16% glycine residues, of about 4 to about 11% serine residues, of about 26 to about 32% arginine residues and of about 47 to about 55% lysine residues. Especially preferred are polypeptide stretches comprising at least one motive according to SEQ ID NO: 47 (KRGSG). More preferred are cationic stretches comprising at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or about 20 motives according to SEQ ID NO: 47 (KRGSG).

[0052] In another preferred embodiment of the present invention the cationic peptide stretch comprises beside the positively charged amino acid residues, in particular lysine and/or arginine residues, hydrophobic amino acid residues, in particular valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, cysteine, alanine, tyrosine, histidine, threonin, serine, proline and glycine residues, more preferably alanine, valine, leucine, isoleucine, phenylalanine, and/or tryptophan residues. Preferred are cationic peptide stretches consisting of about 70% to about 100%, or about 80% to about 95%, or about 85% to about 90% positively charged amino acid residues, in particular lysine and/or arginine residues and of about 0% to about 30%, or about 5% to about 20%, or about 10% to about 20% hydrophobic amino acid residues, valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, cysteine, alanine, tyrosine, histidine, threonin, serine, proline and glycine residues, more preferably alanine, valine, leucine, isoleucine, phenylalanine, and/or tryptophan residues.

[0053] Especially preferred are peptide stretches selected from the group consisting of the following sequences:

TABLE-US-00002 TABLE 2 peptide stretch length SEQ ID NO: KRKKRK 6 SEQ ID NO: 24 KRKKRKKRK 9 SEQ ID NO: 13 RRRRRRRRR 9 SEQ ID NO: 25 KKKKKKKK 8 SEQ ID NO: 26 KRKKRKKRKK 10 SEQ ID NO: 27 KRKKRKKRKKRK 12 SEQ ID NO: 28 KRKKRKKRKKRKKR 14 SEQ ID NO: 29 KKKKKKKKKKKKKKKK 16 SEQ ID NO: 30 KRKKRKKRKKRKKRKKRK 18 SEQ ID NO: 31 KRKKRKKRKKRKKRKKRKK 19 SEQ ID NO: 32 RRRRRRRRRRRRRRRRRRR 19 SEQ ID NO: 33 KKKKKKKKKKKKKKKKKKK 19 SEQ ID NO: 34 KRKKRKKRKRSKRKKRKKRK 20 SEQ ID NO: 35 KRKKRKKRKRSKRKKRKKRKK 21 SEQ ID NO: 36 KRKKRKKRKKRKKRKKRKKRK 21 SEQ ID NO: 37 KRKKRKKRKRGSGKRKKRKKRK 22 SEQ ID NO: 38 KRKKRKKRKRGSGSGKRKKRKKRK 24 SEQ ID NO: 39 KRKKRKKRKKRKKRKKRKKRKKRKK 25 SEQ ID NO: 40 KRKKRKKRKRSKRKKRKKRKRSKRKKRKKRK 31 SEQ ID NO: 41 KRKKRKKRKRGSGSGKRKKRKKRKGSGSGKRKKRKKRK 38 SEQ ID NO: 42 KRKKRKKRKKRKKRKKRKKRKKRKKRKKRKKRKKRKKRK 39 SEQ ID NO: 43 KRKKRKKRKRSKRKKRKKRKRSKRKKRKKRKRSKRKKRKKRK 42 SEQ ID NO: 44

[0054] In a further aspect of the present invention the fused peptide stretch is an amphipatic peptide, which comprises one or more of the positively charged amino acid residues of lysine, arginine and/or histidine, combined to one or more of the hydrophobic amino acid residues of valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, cysteine, alanine, tyrosine, histidine, threonin, serine, proline and/or glycine. Side chains of the amino acid residues are oriented in order that cationic and hydrophobic surfaces are clustered at opposite sides of the peptide. Preferably, more than about 30, 40, 50, 60 or 70% of the amino acids in said peptide are positively charged amino acids. Preferably, more than about 30, 40, 50, 60 or 70%, of the amino acid residues in said peptide are hydrophobic amino acid residues. Advantageously, the amphipathic peptide is fused at the N-terminal and/or the C-terminal end of the enzyme having cell wall degrading activity, thus enhancing the amphipathicity of the latter proteins.

[0055] In another embodiment of the invention, the amphipathic peptide fused to the enzyme consists of at least 5, more preferably at least of 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 amino acid residues. In a preferred embodiment at least about 30, 40, 50, 60 or 70% of the said amino acid residues of the amphipatic peptide are either arginine or lysine residues and/or at least about 30, 40, 50, 60 or 70% of the said amino acid residues of the amphipathic peptide are of the hydrophobic amino acids valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, cysteine, alanine, tyrosine, histidine, threonin, serine, proline and/or glycine.

[0056] Preferred amphipatic peptides are Pleurocidin according to SEQ ID NO:1, Cecropin P1 according to SEQ ID NO:2, Buforin II according to SEQ ID NO:3, Buforin I according to SEQ ID NO:23 and Magainin according to SEQ ID NO:4. Further preferred amphipatic peptides are Cathelidicine e.g. LL-37 according to SEQ ID NO:5, Nigrocine 2 according to SEQ ID NO: 48 and Ascaphine 5 according to SEQ ID NO:49.

[0057] In a further aspect of the present invention the fused peptide stretch is an antimicrobial peptide, which comprises a positive net charge and around 50% hydrophobic amino acids. The antimicrobial peptides are amphipathic, with a length of about 12 to about 50 amino acid residues.

[0058] Examples for antimicrobial peptides are listed in the following table.

TABLE-US-00003 TABLE 3 Peptid Sequenz LL-37 LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES SEQ ID NO: 5 SMAP-29 RGLRRLGRKIAHGVKKYGPTVLRIIRIAG SEQ ID NO: 6 Indolicidin ILPWKWPWWPWRR SEQ ID NO: 7 Protegrin RGGRLCYCRRRFCVCVGR SEQ ID NO: 8 Cecropin P1 SWLSKTAKKLENSAKKRISEGIAIAIQGGPR SEQ ID NO: 2 Magainin GIGKFLHSAKKFGKAFVGEIMNS SEQ ID NO: 4 Pleurocidin GWGSFFKKAAHVGKHVGKAALTHYL SEQ ID NO: 1 Cecropin A GGLKKLGKKLEGAGKRVFNAAEKALPVVAGAKALRK SEQ ID NO: 9 (A.aegypti) Cecropin A GWLKKIGKKIERVGQHTRDATIQGLGIPQQAANVAATARG SEQ ID NO: 10 (D.melanogaster) Buforin II TRSSRAGLQFPVGRVHRLLRK SEQ ID NO: 3 Sarcotoxin IAGWLKKIGKKIERVGQHTRDATIQGLGIAQQAANVAATAR SEQ ID NO: 11 Apidaecine ANRPVYIPPPRPPHPRL SEQ ID NO: 50 Ascaphine 5 GIKDWIKGAAKKLIKTVASHIANQ SEQ ID NO: 49 Nigrocine 2 GLLSKVLGVGKKVLCGVSGLVC SEQ ID NO: 48 Pseudin 1 GLNTLKKVFQGLHEAIKLINNHVQ SEQ ID NO: 51 Ranalexin FLGGLIVPAMICAVTKKC SEQ ID NO: 52 Melittin GIGAVLKVLTTGLPALISWIKRKRQQ SEQ ID NO: 53

[0059] In a further aspect of the present invention the fused peptide stretch is a sushi peptide which is described by Ding J L, Li P, Ho B Cell Mol Life Sci. 2008 April; 65(7-8):1202-19. The Sushi peptides: structural characterization and mode of action against Gram-negative bacteria. Especially preferred is the sushi 1 peptide according to SEQ ID NO:54.

[0060] Preferred sushi peptides are sushi peptides 51 and S3 and multiples thereof; FASEB J. 2000 September; 14(12):1801-13.

[0061] In a further aspect of the present invention the fused peptide stretch is a defensin, preferably Cathelicidine, Cecropin P1, Cecropin A or Magainin II.

[0062] In a further aspect of the present invention the fused peptide stretch is a hydrophobic peptide e.g. Apidaecine having the amino acid sequence according to SEQ ID NO: 50, WLBU2-Variant having the amino acid sequence according to SEQ ID NO: 55 and Walmagh1 having the amino acid sequence according to SEQ ID NO: 56. The hydrophobic peptide having the amino acid sequence Phe-Phe-Val-Ala-Pro (SEQ ID NO: 12) is not part of the present invention.

[0063] In another preferred embodiment of the present invention the peptide stretches of the fusion protein according to the present invention comprise modifications and/or alterations of the amino acid sequences. Such alterations and/or modifications may comprise mutations such as deletions, insertions and additions, substitutions or combinations thereof and/or chemical changes of the amino acid residues, e.g. biotinylation, acetylation, peglyation, chemical changes of the amino-, SH- or carboxyl-groups.

[0064] Especially preferred are fusion proteins according to the SEQ ID NOs: 63 to 90 and the fusion proteins selected from the group consisting of the following fusion proteins:

TABLE-US-00004 TABLE 4 Peptide stretch Fusion Fusion Enzyme (N-terminal unless protein protein part otherwise indicated) P1-E1 SEQ ID NO: 63 Cpl-1 Ascaphine 5 (SEQ ID NO: 57) (SEQ ID NO: 49) P2-E1 SEQ ID NO: 64 Cpl-1 Apiadaecine (SEQ ID NO: 57) (SEQ ID NO: 50) P3-E1 SEQ ID NO: 65 Cpl-1 Nigrocine 2 (SEQ ID NO: 57) (SEQ ID NO: 48) P4-E1 SEQ ID NO: 66 Cpl-1 Pseudin 1 (SEQ ID NO: 57) (SEQ ID NO: 51) P7-E1 SEQ ID NO: 67 Cpl-1 Ranalexin (SEQ ID NO: 57) (SEQ ID NO: 52) P8-E1 SEQ ID NO: 68 Cpl-1 WLBU2-Variant (SEQ ID NO: 57) (SEQ ID NO: 55) P9-E1 SEQ ID NO: 69 Cpl-1 Sushi 1 (SEQ ID NO: 57) (SEQ ID NO: 54) P10-E1 SEQ ID NO: 70 Cpl-1 Melittin (SEQ ID NO: 57) (SEQ ID NO: 53) P11-E1 SEQ ID NO: 71 Cpl-1 LL-37 (SEQ ID NO: 57) (SEQ ID NO: 5) P12-E1 SEQ ID NO: 72 Cpl-1 Indolicidin (SEQ ID NO: 57) (SEQ ID NO: 7) P13-E1 SEQ ID NO: 73 Cpl-1 SMAP-29 (SEQ ID NO: 57) (SEQ ID NO: 6) P14-E1 SEQ ID NO: 74 Cpl-1 Protegrin (SEQ ID NO: 57) (SEQ ID NO: 8) P15-E1 SEQ ID NO: 75 Cpl-1 Cecropin P1 (SEQ ID NO: 57) (SEQ ID NO: 2) P16-E1 SEQ ID NO: 76 Cpl-1 Magainin (SEQ ID NO: 57) (SEQ ID NO: 4) P17-E1 SEQ ID NO: 77 Cpl-1 Pleurocidin (SEQ ID NO: 57) (SEQ ID NO: 1) P18-E1 SEQ ID NO: 78 Cpl-1 Cecropin A (SEQ ID NO: 57) (A. aegypti) (SEQ ID NO: 9) P19-E1 SEQ ID NO: 79 Cpl-1 Cecropin A (SEQ ID NO: 57) (D. melanogaster) (SEQ ID NO: 10) P20-E1 SEQ ID NO: 80 Cpl-1 Buforin II (SEQ ID NO: 57) (SEQ ID NO: 3) P21-E1 SEQ ID NO: 81 Cpl-1 Sarcotoxin IA (SEQ ID NO: 57) (SEQ ID NO: 11) P5-E1 SEQ ID NO: 82 Cpl-1 PK (SEQ ID NO: 57) (SEQ ID NO: 13) P22-E2 SEQ ID NO: 83 Ply511 Pentapeptid (SEQ ID NO: 58) (SEQ ID NO: 12) P5-E7 SEQ ID NO: 84 LysK PK (N-terminal) (SEQ ID NO: 59) (SEQ ID NO: 13) P6-E7 SEQ ID NO: 85 LysK PK2 (SEQ ID NO: 59) (SEQ ID NO: 31) P5-E8 SEQ ID NO: 86 Lysostaphin PK (C-terminal ) (SEQ ID NO: 60) (SEQ ID NO: 13) P6-E8 SEQ ID NO: 87 Lysostaphin PK2 (SEQ ID NO: 60) (SEQ ID NO: 31) P23-E9 SEQ ID NO: 88 PA6-gp20 Walmaghl (SEQ ID NO: 61) (SEQ ID NO: 56) P5-E7 SEQ ID NO: 89 LysK PK (C-terminal) (SEQ ID NO: 59) (SEQ ID NO: 13) P5-E8 SEQ ID NO: 90 Lysostaphin PK (N-terminal) (SEQ ID NO: 60) (SEQ ID NO: 13)

[0065] The fusion protein according to the present invention, and thus in particular the especially preferred fusion proteins according to SEQ ID NO:63 to 90, may additional comprise a methionine on the N-terminus.

[0066] The fusion protein according to the present invention, and thus in particular the especially preferred fusion proteins according to SEQ ID NO:63 to 90, may additional comprise a tag e.g. for purification. Preferred is a His₆-tag, preferably at the C-terminus of the fusion protein. Said tag can be linked to the fusion protein by additional amino acid residues e.g. due to cloning reasons. Preferably said tag can be linked to the fusion protein by at least 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 additional amino acid residues. In a preferred embodiment the fusion protein comprises a His₆-tag at its C-terminus linked to the fusion protein by the additional amino acid residues lysine and glycine (Lys-Gly) or leucine and glutamic acid (Leu-Glu). In another preferred embodiment the fusion protein comprises a His₆-tag at its N-terminus linked to the fusion protein by the additional amino acid residues lysine and glycine (Lys-Gly) or leucine and glutamic acid (Leu-Glu). In a more preferred embodiment the fusion protein comprises a His₆-tag at its N-terminus linked to the fusion protein by the additional amino acid residues leucine and glutamic acid (Leu-Glu). In another preferred embodiment the fusion protein comprises a His₆-tag at its C-terminus linked to the fusion protein by the additional amino acid residues leucine and glutamic acid (Leu-Glu).

[0067] In a more preferred embodiment the fusion protein comprises a His₆-tag at its C-terminus linked to the fusion protein by the additional amino acid residues leucine and glutamic acid (Leu-Glu) and the peptide stretch of the fusion protein according to the invention is linked to the N-terminus of the enzyme by the additional amino acid residues glycine and serine (Gly-Ser). In another preferred embodiment the fusion protein comprises a His₆-tag at its C-terminus linked to the fusion protein by the additional amino acid residues leucine and glutamic acid (Leu-Glu) and the peptide stretch of the fusion protein according to the invention is linked to the N-terminus of the enzyme by the additional amino acid residues glycine and serine (Gly-Ser) and the fusion protein comprises on the N-terminus the additional amino acid residues methionine (Met) or methionine and glycine (Met-Gly) or alanine, methionine and glycine (Ala-Met-Gly). Preferably the fusion proteins are according to SEQ ID NO: 108 to 123.

[0068] In another preferred embodiment the fusion protein comprises a His₆-tag at its N-terminus, wherein the His₆-tag further comprises on its N-terminus the additional amino acids serine and serine (Ser-Ser) or methionine and glycine (Met-Gly) or methionine, glycine, serine and serine (Met-Gly-Ser-Ser).

[0069] In another preferred embodiment the fusion protein comprises a His₆-tag at its N-terminus linked to the fusion protein by the additional amino acid residues serine, serine, glycine, leucine, valine, proline, arginine, glycine, serine and histidine (Ser-Ser-Gly-Leu-Val-Pro-Arg-Gly-Ser-His). In another preferred embodiment the fusion protein comprises a His₆-tag at its N-terminus linked to the fusion protein by the additional amino acid residues serine, serine, glycine, leucine, valine, proline, arginine, glycine, serine, histidine and methionine (Ser-Ser-Gly-Leu-Val-Pro-Arg-Gly-Ser-His-Met). In another preferred embodiment the fusion protein comprises a His₆-tag at its N-terminus linked to the fusion protein by the additional amino acid residues serine, serine, glycine, leucine, valine, proline, arginine, glycine, serine and histidine (Ser-Ser-Gly-Leu-Val-Pro-Arg-Gly-Ser-His) or serine, serine, glycine, leucine, valine, proline, arginine, glycine, serine, histidine and methionine (Ser-Ser-Gly-Leu-Val-Pro-Arg-Gly-Ser-His-Met) and the peptide stretch of the fusion protein according to the invention is linked to the C-terminus of the enzyme by the additional amino acid residue serine. In another preferred embodiment the fusion protein comprises a His₆-tag at its N-terminus linked to the fusion protein by the additional amino acid residues serine, serine, glycine, leucine, valine, proline, arginine, glycine, serine and histidine (Ser-Ser-Gly-Leu-Val-Pro-Arg-Gly-Ser-His) or serine, serine, glycine, leucine, valine, proline, arginine, glycine, serine, histidine and methionine (Ser-Ser-Gly-Leu-Val-Pro-Arg-Gly-Ser-His-Met) and the peptide stretch of the fusion protein according to the invention is linked to the C-terminus of the enzyme by the additional amino acid residue serine and the His6-tag comprises on the N-terminus the additional amino acid residues serine and serine (Ser-Ser) or methionine, glycine, serine and serine (Met-Gly-Ser-Ser) or methionine and serine (Met-Ser). Preferably the fusion proteins are according to SEQ ID NO: 122 and 123.

[0070] Fusion proteins are constructed by linking at least two nucleic acid sequences using standard cloning techniques as described e.g. by Sambrook et al. 2001, Molecular Cloning: A Laboratory Manual. Such a protein may be produced, e.g., in recombinant DNA expression systems. Such fusion proteins according to the present invention can be obtained by fusing the nucleic acids for endolysin and the respective peptide stretch.

[0071] The fusion proteins according to the present invention may be fused or linked to other additional proteins. Example for this other additional protein is thioredoxin.

[0072] The present invention further relates to an isolated nucleic acid molecule encoding the fusion protein according to the present invention. The present invention further relates to a vector comprising the nucleic acid molecule according to the present invention. Said vector may provide for the constitutive or inducible expression of said fusion protein according to the present invention.

[0073] The invention also relates to a method for obtaining said fusion proteins from a micro-organism, such as a genetically modified suitable host cell which expresses said fusion proteins. Said host cell may be a micro-organism such as bacteria or yeast or an animal cell as e.g. a mammalian cell, in particular a human cell. In one embodiment of the present invention the host cell is a Pichia pastoris cell. The host may be selected due to mere biotechnological reasons, e.g. yield, solubility, costs, etc. but may be also selected from a medical point of view, e.g. a non-pathological bacteria or yeast, human cells. Another aspect of the present invention is related to a method for genetically transforming a suitable host cell in order to obtain the expression of the fusion proteins according to the invention wherein the host cell is genetically modified by the introduction of a genetic material encoding said fusion proteins into the host cell and obtain their translation and expression by genetic engineering methods well known by the man skilled in the art.

[0074] In a further aspect the present invention relates to a composition, preferably a pharmaceutical composition, comprising a fusion protein according to the present invention and/or a host transformed with a nucleic acid molecule or a vector comprising a nucleotide sequence encoding a fusion protein according to the present invention.

[0075] The present invention also relates to a fusion protein according to the present invention and/or a host transformed with a nucleic acid comprising a nucleotide sequence encoding a fusion protein according to the present invention for use as a medicament. In a further aspect the present invention relates to the use of a fusion protein according to the present invention and/or a host transformed with a vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a modified, fusion protein according to the present invention in the manufacture of a medicament for the treatment and/or prevention of a disorder, disease or condition associated with Gram-positive bacteria. In particular the treatment and/or prevention of the disorder, disease or condition may be caused by Gram-positive bacteria of bacterial groups, families, genera or species comprising strains pathogenic for humans or animals like Listeria monocytogenes, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus mutans, Streptococcus equi, Clostridium difficile, Clostridium botulinum, Clostridium tetani, Clostridium perfringens, Bacillus anthracis, Bacillus cereus, Propionibacterium acnes, Mycobacterium avium, Mycobacterium tuberculosis, Corynebacterium diphteriae, Mycoplasma pneumoniae, Actinomyces.

[0076] The present invention further relates to a medicament comprising a fusion protein according to the present invention and/or a host transformed with a nucleic acid comprising a nucleotide sequence encoding a fusion protein according to the present invention.

[0077] In a further aspect the present invention relates to a method of treating a disorder, disease or condition in a subject in need of treatment and/or prevention, which method comprises administering to said subject an effective amount of a fusion protein according to the present invention and/or an effective amount of a host transformed with a nucleic acid comprising a nucleotide sequence encoding a fusion protein according to the present invention or a composition according to the present invention. The subject may be a human or an animal.

[0078] In particular said method of treatment may be for the treatment and/or prevention of infections of the skin, of soft tissues, the respiratory system, the lung, the digestive tract, the eye, the ear, the teeth, the nasopharynx, the mouth, the bones, the vagina, of wounds of bacteraemia and/or endocarditis caused by Gram-positive bacteria, in particular by the Gram-positive bacteria as listed above.

[0079] The dosage and route of administration used in a method of treatment (or prophylaxis) according to the present invention depends on the specific disease/site of infection to be treated. The route of administration may be for example oral, topical, nasopharyngeal, parenteral, intravenous, rectal or any other route of administration.

[0080] For application of a fusion protein according to the present invention and/or an effective amount of a host transformed with a nucleic acid comprising a nucleotide sequence encoding a fusion protein according to the present invention or a composition according to the present invention to a site of infection (or site endangered to be infected) a formulation may be used that protects the active compounds from environmental influences such as proteases, oxidation, immune response etc., until it reaches the site of infection. Therefore, the formulation may be capsule, dragee, pill, powder, suppository, emulsion, suspension, gel, lotion, cream, salve, injectable solution, syrup, spray, inhalant or any other medical reasonable galenic formulation. Preferably, the galenic formulation may comprise suitable carriers, stabilizers, flavourings, buffers or other suitable reagents. For example, for topical application the formulation may be a lotion, cream, gel, salve or plaster, for nasopharyngeal application the formulation may be saline solution to be applied via a spray to the nose. For oral administration in case of the treatment and/or prevention of a specific infection site e.g. in the intestine, it can be necessary to protect a fusion protein according to the present invention from the harsh digestive environment of the gastrointestinal tract until the site of infection is reached. Thus, bacteria as carrier, which survive the initial steps of digestion in the stomach and which secret later on a fusion protein according to the present invention into the intestinal environment can be used.

[0081] In a specific embodiment of the present invention the use of a fusion protein according to the present invention and/or a host transformed with a vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a fusion protein according to the present invention in the manufacture of a medicament for the treatment and/or prevention of a disorder, disease or condition caused by Listeria monocytogenes, in particular Granulomatosis infantiseptica (listeriosis of newborns), mononucleosis, conjunctivitis, meningitis, granulomatosis septica and the listeriosis of pregnant women.

[0082] In another specific embodiment of the present invention the disorder, disease or condition is caused by Staphylococcus aureus, in particular infections of the skin like pyoderma, particularly folliculitis, furuncle, carbuncle, abscesses of the sweat glands and pemphigus, and like scaled skin syndrome. The scaled skin syndrome can appear in three clinical pictures: dermatitis exfoliativa, impetigo bullosa and scarlatiniform erythroderma. Moreover the disorder, disease or condition caused by Staphylococcus aureus is Staphylococcus pneumonia, hospitalism, in particular surgical wound infections, mastitis puerperalis and enterokolitis, and food poisonings.

[0083] In another specific embodiment of the present invention the disorder, disease or condition is caused by Streptococcus pyogenes, in particular tonsillitis, pharyngitis, scarlet, erysipelas, rheumatic fever and acute glomerulonephritis.

[0084] In another specific embodiment of the present invention the disorder, disease or condition is caused by Streptococcus pneumoniae, in particular pneumonia, ulcus serpens corneae, otitis media, meningitis, peritonitis, mastoiditis and osteomyelitis.

[0085] In another specific embodiment of the present invention the disorder, disease or condition is caused by Clostridium perfringens, in particular gas gangrene, enteritis necroticans ulcerosa and food poisonings.

[0086] In another specific embodiment of the present invention the disorder, disease or condition is caused by Clostridium botulinum, in particular botulism.

[0087] In another specific embodiment of the present invention the disorder, disease or condition is caused by Clostridium difficile, in particular pseudomembranoes enterokolitis.

[0088] In another specific embodiment of the present invention the disorder, disease or condition is caused by Bacillus anthracis, in particular cutaneous anthrax, inhalation anthrax, and gastrointestinal anthrax.

[0089] In another specific embodiment of the present invention the disorder, disease or condition is caused by Enterococcus faecalis or E. faecium, like nosokomial infections, and endokarditis.

[0090] In another specific embodiment of the present invention the disorder, disease or condition is caused by Bacillus cereus, in particular food poisonings, bronchial pneumonia, septicaemia and meningitis.

[0091] In another specific embodiment of the present invention the disorder, disease or condition is caused by Mycobacterium avium, Mycobacterium paratuberculosis and Mycobacterium tuberculosis, in particular tuberculosis.

[0092] In another specific embodiment of the present invention the disorder, disease or condition is caused by Mycoplasma pneumoniae, in particular pneumonia, diseases of the upper respiratory tract and inflammations of the ear drum.

[0093] In another specific embodiment of the present invention the disorder, disease or condition is caused by Actinomyces, in particular actinomycosis in human, cattle, cat and dog.

[0094] In another specific embodiment of the present invention the disorder, disease or condition is caused by Corynebacterium diphteriae, in particular localized diphtheria of the tonsils, the nose, the nasopharynx or the middle ear, progressive diphtheria of the larynx, the trachea and the bronchi, toxic or maligne diphtheria, skin and wound diphtheria.

[0095] Preferably, a fusion protein according to the present invention is used for medical treatment, if the infection to be treated (or prevented) is caused by multiresistant bacterial strains, in particular by strains resistant against one or more of the following antibiotics: streptomycin, tetracycline, cephalothin, penicillin, gentamicin, cefotaxime, cephalosporin, ceftazidime or imipenem. Furthermore, a fusion protein according to the present invention can be used in methods of treatment by administering it in combination with conventional antibacterial agents, such as antibiotics, lantibiotics, bacteriocins or endolysins, etc.

[0096] The present invention also relates to a pharmaceutical pack comprising one or more compartments, wherein at least one compartment comprises one or more fusion protein according to the present invention and/or one or more hosts transformed with a nucleic acid comprising a nucleotide sequence encoding a fusion protein according to the present invention or a composition according to the present invention,

[0097] In another aspect the present invention relates to a process of preparation of a pharmaceutical composition, said process comprising admixing one or more fusion protein according to the present invention and/or one or more hosts transformed with a nucleic acid comprising a nucleotide sequence encoding a fusion protein according to the present invention with a pharmaceutically acceptable diluent, excipient or carrier.

[0098] In an even further aspect the composition according to the present invention is a cosmetic composition. Several bacterial species can cause irritations on environmentally exposed surfaces of the patient's body such as the skin. In order to prevent such irritations or in order to eliminate minor manifestations of said bacterial pathogens, special cosmetic preparations may be employed, which comprise sufficient amounts of the fusion protein according to the present invention in order to degrade already existing or freshly settling pathogenic Gram-positive bacteria.

[0099] In a further aspect the present invention relates to the fusion protein according to the present invention for use as diagnostic means in medicinal, food or feed or environmental diagnostics, in particular as a diagnostic means for the diagnostic of bacteria infection caused in particular by Gram-positive bacteria. In this respect the fusion protein according to the present invention may be used as a tool to specifically degrade pathogenic bacteria, in particular Gram-positive pathogenic bacteria. The degradation of the bacterial cells by the fusion protein according to the present invention can be supported by the addition of detergents like Triton X-100 or other additives which weaken the bacterial cell envelope like polymyxin B. Specific cell degradation is needed as an initial step for subsequent specific detection of bacteria using nucleic acid based methods like PCR, nucleic acid hybridization or NASBA (Nucleic Acid Sequence Based Amplification), immunological methods like IMS, immunofluorescence or ELISA techniques, or other methods relying on the cellular content of the bacterial cells like enzymatic assays using proteins specific for distinct bacterial groups or species (e.g. β-galactosidase for enterobacteria, coagulase for coagulase positive strains).

[0100] In a further aspect the present invention relates to the use of the fusion protein according to the present invention for the treatment or prevention of Gram-positive bacterial contamination of foodstuff, of food processing equipment, of food processing plants, of surfaces coming into contact with foodstuff such as shelves and food deposit areas and in all other situations, where pathogenic, facultative pathogenic or other undesirable bacteria can potentially infest food material, of medical devices and of all kind of surfaces in hospitals and surgeries.

[0101] In particular, a fusion protein of the present invention may be used prophylactically as sanitizing agent. Said sanitizing agent may be used before or after surgery, or for example during hemodialysis. Moreover, premature infants and immunocompromised persons, or those subjects with need for prosthetic devices may be treated with a fusion protein according to the present invention. Said treatment may be either prophylactically or during acute infection. In the same context, nosocomial infections, especially by antibiotic resistant strains like Methicillin-resistant Staphylococcus aureus, Vancomycin-resistant Enterococcus faecalis, Vancomycin-resistant Enterococcus faecium, Streptococcus pneumoniae, Propionibacterium acnes, multidrug-resistant Mycobacterium tuberculosis, may be treated prophylactically or during acute phase with a fusion protein of the present invention. Therefore, a fusion protein according to the present invention may be used as a disinfectant also in combination with other ingredients useful in a disinfecting solution like detergents, tensids, solvents, antibiotics, lanthibiotics, or bacteriocins.

[0102] For the use of the fusion protein according to the present invention as a disinfectant e.g. in hospital, dental surgery, veterinary, kitchen or bathroom, the fusion protein can be prepared in a composition in form of e.g. a fluid, a powder, a gel, or an ingredient of a wet wipe or a disinfection sheet product. Said composition may additionally comprise suitable carrier, additives, diluting agents and/or excipients for its respective use and form, respectively, --but also agents that support the antimicrobial activity like EDTA or agents enhance the antimicrobial activity of the fusion proteins. The fusion protein may also be used with common disinfectant agents like, Alcohols, Aldehydes, Oxidizing agents, Phenolics, Quaternary ammonium compounds or UV-light. For disinfecting for example surfaces, objects and/or devices the fusion protein can be applied on said surfaces, objects and/or devices. The application may occur for instance by wetting the disinfecting composition with any means such as a cloth or rag, by spraying, pouring. The fusion proteins may be used in varying concentration depending on the respective application and the "reaction time" intended to obtain full antimicrobial activity.

[0103] Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter, however, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.

[0104] The following examples explain the present invention but are not considered to be limiting. Unless indicated differently, molecular biological standard methods were used, as e.g., described by Sambrock et al., 1989, Molecular Cloning: A Laboratory Manual, 2nd edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.

EXAMPLE 1

Cloning, Expression and Purification of Cpl-1, Ply511, LysK, Lysostaphin (Lss) and PA6-gp20 Enzymes Modified with Various Peptide Stretches on the N-Terminus or the C-Terminus

Enzymes

[0105] Cpl-1 according to SEQ ID NO: 57 is an endolysin originating from Streptococcus pneumoniae phage Cpl-1. The endolysin Cpl-1 is encoded by the nucleic acid molecule according to SEQ ID NO: 91. The nucleic acid molecule according to SEQ ID NO: 91 was synthetically produced with a BamH I (5'-GGA TCC-3') restriction site at the 5'-end of the nucleic acid molecule and an Xho I (5'-CTC GAG-3') restriction site at the 3'-end of the nucleic acid molecule.

[0106] Ply511 according to SEQ ID NO: 58 is an endolysin originating from Listeria monocytogenes phage A511. The endolysin Ply511 is encoded by the nucleic acid molecule according to SEQ ID NO: 92. The nucleic acid molecule according to SEQ ID NO: 92 was synthetically produced with a BamH I (5'-GGA TCC-3') restriction site at the 5'-end of the nucleic acid molecule and an Xho I (5'-CTC GAG-3') restriction site at the 3'-end of the nucleic acid molecule.

[0107] LysK according to SEQ ID NO: 59 is an endolysin originating from Staphylococcus aureus phage K. The endolysin LysK is encoded by the nucleic acid molecule according to SEQ ID NO: 93. The nucleic acid molecule according to SEQ ID NO: 93 was synthetically produced with a BamH I (5'-GGA TCC-3') restriction site at the 5'-end of the nucleic acid molecule and an Xho I (5'-CTC GAG-3') restriction site at the 3'-end of the nucleic acid molecule.

[0108] Lysostaphin (Lss) according to SEQ ID NO: 60 is a bacteriocin originating from Staphylococcus simulans. The bacteriocin Lss is encoded by the nucleic acid molecule according to SEQ ID NO: 94. The nucleic acid molecule according to SEQ ID NO: 94 was synthetically produced with a BamH I (5'-GGA TCC-3') restriction site at the 5'-end of the nucleic acid molecule and an Xho I (5'-CTC GAG-3') restriction site at the 3'-end of the nucleic acid molecule.

[0109] PA6-gp20_ according to SEQ ID NO: 61 is an endolysin originating from Propionibacterium acnes phage. The endolysin PA6-gp20 is encoded by the nucleic acid molecule according to SEQ ID NO: 123. The nucleic acid molecule according to SEQ ID NO: 123 was synthetically produced with a BamH I (5'-GGA TCC-3') restriction site at the 5'-end of the nucleic acid molecule and an Xho I (5'-CTC GAG-3') restriction site at the 3'-end of the nucleic acid molecule.

[0110] The following peptide stretches in table 5 were used for production of fusion proteins with the enzymes Cpl-1, Ply511, LysK, Lysostaphin (Lss) and PA6-gp20:

TABLE-US-00005 TABLE 5 Nucleic acid molecule Peptide stretch encoding the peptide stretch Pseudin 1 SEQ ID NO: 95 (SEQ ID NO: 51) WLBU2-Variant SEQ ID NO: 96 (SEQ ID NO: 55) LL-37 SEQ ID NO: 97 (SEQ ID NO: 5) Indolicidin SEQ ID NO: 98 (SEQ ID NO: 7) Magainin SEQ ID NO: 99 (SEQ ID NO: 4) Pleurocidin SEQ ID NO: 100 (SEQ ID NO: 1) Cecropin A SEQ ID NO: 101 (A. aegypti) (SEQ ID NO: 9) Buforin II SEQ ID NO: 102 (SEQ ID NO: 3) Sarcotoxin IA SEQ ID NO: 103 (SEQ ID NO: 11) PK SEQ ID NO: 104 (SEQ ID NO: 13) Pentapeptide SEQ ID NO: 105 (SEQ ID NO: 12) PK2 SEQ ID NO: 106 (SEQ ID NO: 31)

[0111] The nucleic acid molecules encoding the respective peptide stretches were synthetically produced with a Nde I (5'-CAT ATG-3') restriction site at the 5'-end of the nucleic acid molecule and a BamH I (5'-GGA TCC-3') restriction site at the 3'-end of the nucleic acid molecule, except the nucleic acid molecule encoding the PK and PK2 for ligation with the bacteriocin Lss, which was produced with a Nco I restriction site plus two additional nucleotides (5'-CCA TGG GC-3') at the 5'-end of the nucleic acid molecule.

[0112] Fusion proteins are constructed by linking at least two nucleic acid sequences using standard cloning techniques as described e.g. by Sambrook et al. 2001, Molecular Cloning: A Laboratory Manual. Therefore the nucleic acid molecules encoding the peptide stretches were cleaved in a digest with the respective restriction enzymes Nde I and BamH I and in case of the nucleic acid molecule encoding the peptide stretch PK and PK2 for ligation with the Lss the digest was performed with the restriction enzymes Nco I and BamH I. Subsequently the cleaved nucleic acids encoding the peptide stretches were ligated into the pET21 b expression vector (Novagen, Darmstadt, Germany), which was also cleaved in a digest with the respective restriction enzymes Nde I and BamH I before. The cleaved nucleic acid molecule encoding the peptide stretch PK and PK2 for ligation with Lss was ligated into a modified pET32 b expression vector (unmodified vector obtainable from Novagen, Darmstadt, Germany), which was also cleaved in a digest with the respective restriction enzymes Nco I and BamH I before. The modification of the pET32b expression vector refers to the deletion of the sequence encoding a S-tag and the central His₆-tag.

[0113] Afterwards, the nucleic acid molecules encoding the enzymes Cpl-1, Ply511, PA6-gp20, LysK and Lss were cleaved in a digest with the restriction enzyme BamH I and Xho I, so that the endolysin could be ligated into the pET21b expression vector (Novagen, Darmstadt, Germany) and the modified pET32 b expression vector, respectively, which were also cleaved in a digest with the respective restriction enzymes BamH I and Xho I before.

[0114] In the case of the peptide stretch PK, which was ligated to the C-terminus of the Lysostaphin and the LysK, the resulting fusion protein has a His₆-tag on the N-terminus, wherein the His₆-tag is linked to the N-terminus by a linker. For the cloning of the respective nucleic acid molecules the pET32 b expression vector (Novagen, Darmstadt, Germany) was used.

[0115] Thus, the nucleic acid molecule encoding the peptide stretch is ligated into the respective vector at the 5'-end of the nucleic acid molecule encoding the respective enzyme. Moreover, the nucleic acid molecule encoding the respective enzyme is ligated into the respective plasmid, so that a nucleic acid molecule encoding a His₆-tag consisting of six histidine residues is associated at the 3'-end of the nucleic acid molecule encoding the endolysin.

[0116] As some fusion proteins may either be toxic upon expression in bacteria, or not homogenous due to protein degradation, the strategy might be to express these fusion proteins fused or linked to other additional proteins. Example for these other additional protein is thioredoxin, which was shown to mediate expression of toxic antimicrobial peptides in E. coli (TrxA mediating fusion expression of antimicrobial peptide CM4 from multiple joined genes in Escherichia coli. Zhou L, Zhao Z, Li B, Cai Y, Zhang S. Protein Expr Purif. 2009 April; 64(2):225-230). In the case of the fusion protein consisting of the N-terminal PK or PK2 peptide and the bacteriocin Lss, the peptide was ligated into the modified pET32 b expression vector, so that an additional thioredoxin is associated at the 5'-end of the peptide. The thioredoxin could be removed from the expressed fusion protein by the use of enterokinase, therefore between the nucleic acid molecule encoding the peptide and the one encoding the thioredoxin is an enterokinase restriction site introduced.

[0117] The sequence of the endolysin-peptide-fusions was controlled via DNA-sequencing and correct clones were transformed into E. coli BL21(DE3) and in E. coli BL21 (DE3) pLysS cells (Novagen, Darmstadt, Germany) for protein expression.

[0118] Recombinant expression of the fusion proteins according to SEQ ID NO: 107 to 122 and 124 is performed in E. coli BL21 (DE3) and E. coli BL21 (DE3) pLysS cells (Novagen, Darmstadt, Germany). The cells were growing until an optical density of OD600 nm of 0.5-0.8 was reached. Then the expression of the fusion protein was induced with 1 mM IPTG (isopropylthiogalactoside) and the expression was performed at 37° C. for a period of 4 hours.

[0119] E. coli BL21 cells were harvested by centrifugation for 20 min at 6000 g and disrupted via sonication on ice. Soluble and insoluble fraction of the E. coli crude extract were separated by centrifugation (Sorvall, SS34, 30 min, 15 000 rpm). All proteins were purified by Ni²+ affinity chromatography (Akta FPLC, GE Healthcare) using the C-terminal His₆-tag, encoded by the pET21 b or pET32b vectors.

[0120] Some proteins were expressed using a modified pET32b vector (S-tag and central His₆-tag deleted) as described above, which fuses thioredoxin on the N-terminus of the proteins of interest. The vector also contains an enterokinase cleavage site right before the protein of interest. This site allows the proteolytic cleavage between thioredoxin and the protein of interest, which can purified via the remaining C-terminal His₆-tag. For antimicrobial function of the fusion protein it may be necessary to remove the thioredoxin by proteolytic cleavage. Therefore the fusion protein was cleaved with 2-4 units/mg recombinant enterokinase (Novagen, Darmstadt, Germany) to remove the thioredoxin following the protocol provided by the manufacturer. After enterokinase cleavage the fusion protein was purified via His₆-tag purification as described below.

[0121] The Ni²+ affinity chromatography is performed in 4 subsequent steps, all at room temperature: [0122] 1. Equilibration of the Histrap FF 5 ml column (GE Healthcare) with up to 10 column volumes of Washing Buffer (20 mM imidazole, 1 M NaCl and 20 mM Hepes on pH 7.4) at a flow rate of 3-5 ml/min [0123] 2. Loading of the total lysate (with wanted fusion protein) on the Histrap FF 5 ml column at a flow rate of 3-5 ml/min. [0124] 3. Washing of the column with up to 10 column volumes of Washing Buffer to remove unbound sample followed by a second washing step with 10% Elution buffer (500 mM imidazole, 0.5 M NaCl and 20 mM Hepes on pH 7.4) at a flow rate of 3-5 ml/min [0125] 4. Elution of bounded fusion proteins from the column with a linear gradient of 4 column volumes of Elution Buffer (500 mM imidazole, 0.5 M NaCl and 20 mM Hepes on pH 7.4) to 100% at a flow rate of 3-5 ml/min

[0126] Purified stock solutions of fusion proteins in Elution Buffer (20 mM Hepes pH 7.4; 0.5 M NaCl; 500 mM imidazole) were at least 90% pure as determined visually on SDS-PAGE gels (data not shown).

EXAMPLE 2

Antimicrobial Activity of Cpl-1 Enzymes Modified with Various Peptide Stretches on the N-Terminus

[0127] The fusion proteins Cpl 1 with the N-terminal peptide stretches Pseudin 1, WLBU2-Variant, LL-37, Indolicidin, Magainin, Pleurocidin, Cecropin A (A. aegypti), Buforin II, Sarcotoxin IA and PK were produced as described in example 1. The antimicrobial activity of said fusion protein against Streptococcus pneumoniae DSMZ 11967 and Streptococcus pneumoniae DSMZ 14378 were tested by using the plating test described below. The measured activity of the fusion protein is shown in Table 6.

[0128] The results presented in Table 6 show high antimicrobial activity of all fusion proteins against Streptococcus pneumoniae DSMZ 11967 and Streptococcus pneumoniae DSMZ 14378.

Plating Assay:

[0129] Exponentially growing cells of e.g. Streptococci, Listeria, Propionibacteria or Staphylococci were taken (1 ml) cooled on ice and washed with distilled water. The bacteria were resuspended in 20 mM Tris pH 7.0, 1 mM MgCl₂, 0.5 M Saccharose. Fusion proteins were diluted in resuspension buffer, adding sucrose to a final concentration of 0.5 M and incubated (final concentration of the fusion protein about 10 μg/ml) with the respective bacteria for 60 minutes at room temperature. After that bacteria were plated on appropriated agar plates (e.g. Streptococci: Columbia blood agar) containing 0.5 M sucrose and the resulting colonies were counted after incubation.

[0130] The residual colonies were counted after an overnight incubation at 37° C. Based on the counted cell numbers the antibacterial activity as logarithmic units (=log₁₀N₀/N_i with N₀=number of untreated cells and N_i=number of treated cells) was calculated. All samples were replicated at least in four fold.

TABLE-US-00006 TABLE 6 Activity Activity against against Strepto- Strepto- Peptide stretch coccus coccus (N-terminal pneumoniae pneumoniae Fusion Enzyme unless otherwise DSMZ DSMZ protein part indicated) 11967 14378 SEQ ID Cpl-1 (SEQ Pseudin 1 +++ +++ NO: 107 ID NO: 57) (SEQ ID NO: 51) SEQ ID Cpl-1 (SEQ WLBU2-Variant ++ ++ NO: 108 ID NO: 57) (SEQ ID NO: 55) SEQ ID Cpl-1 (SEQ LL-37 +++ +++ NO: 109 ID NO: 57) (SEQ ID NO: 5) SEQ ID Cpl-1 (SEQ Indolicidin +++ +++ NO: 110 ID NO: 57) (SEQ ID NO: 7) SEQ ID Cpl-1 (SEQ Magainin +++ +++ NO: 111 ID NO: 57) (SEQ ID NO: 4) SEQ ID Cpl-1 (SEQ Pleurocidin +++ +++ NO: 112 ID NO: 57) (SEQ ID NO: 1) SEQ ID Cpl-1 (SEQ Cecropin A +++ +++ NO: 113 ID NO: 57) (A. aegypti) (SEQ ID NO: 9) SEQ ID Cpl-1 (SEQ Buforin II +++ +++ NO: 114 ID NO: 57) (SEQ ID NO: 3) SEQ ID Cpl-1 (SEQ Sarcotoxin IA +++ +++ NO: 115 ID NO: 57) (SEQ ID NO: 11) SEQ ID Cpl-1 (SEQ PK +++ +++ NO: 116 ID NO: 57) (SEQ ID NO: 13) Abbreviations: +: 1 log; ++: 2-3 log; +++: 4 or more logs.

EXAMPLE 3

Antimicrobial Activity of Ply511 Enzyme Modified with the Pentapeptide on the N-Terminus

[0131] The fusion protein Ply511 with the N-terminal peptide stretch pentapeptide according to SEQ ID NO: 12 was produced as described in example 1. The antimicrobial activity of said fusion protein against Listeria monocytogenes DSMZ 15675 and Listeria monocytogenes DSMZ 20600 was tested by using the plating test described in example 2. The measured activity of the fusion protein is shown in Table 7.

[0132] The results presented in Table 7 show high antimicrobial activity of the fusion protein pentapeptide: Ply511 against Listeria monocytogenes DSMZ 15675 and Listeria monocytogenes DSMZ 20600.

TABLE-US-00007 TABLE 7 Activity Activity against against Listeria Listeria Peptide stretch mono- mono- (N-terminal cytogenes cytogenes Fusion unless otherwise DSMZ DSMZ protein Enzyme part indicated) 15675 20600 SEQ ID Ply511 Pentapeptid +++ +++ NO: 117 (SEQ ID NO: 58) (SEQ ID NO: 12) Abbreviations: +: 1 log; ++: 2-3 log; +++: 4 or more logs

EXAMPLE 4

Antimicrobial Activity of Lss and LysK Enzyme Modified with Polycationic Peptides on the N-Terminus or C-Terminus

[0133] The fusion proteins Lss and LysK, respectively, with the N-terminal peptide stretch PK according to SEQ ID NO: 13, the fusion protein Lss with the N-terminal peptide stretch PK2 according to SEQ ID NO:31, as well as the fusion proteins Lss and LysK, respectively, with the C-terminal peptide stretch PK were produced as described in example 1. The antimicrobial activity of said fusion proteins against Staphylococcus aureus DSMZ 346 and Staphylococcus epidermidis DSMZ 20041 was tested by using the plating test described in example 2, as well as by using the lysis test as described in the following.

Lysis Test

[0134] The Lysis test was used for the modified LysK and Lysostaphins to examine the antimicrobial effect of these fusion proteins.

[0135] Staphylococcal cells of were grown in BHI medium until and optical density at 600 nm of 0.7-1 was reached indicating exponential growth. Cells were harvested by centrifugation and resuspended in lysis buffer (20 mM Tris-HCl (pH 7.4), 60 mM NaCl, 2 mM CaCl₂. Cells were resuspended at an optical density at 600 nm of 1.0 and incubated with fusion proteins. Activity was measured spectrophotometrically at 600 nm.

[0136] The measured activity of the fusion protein is shown in Table 8.

[0137] The results presented in Table 8 show high antimicrobial activity of the fusion proteins Lss with the N-terminal peptide PK or PK2 against Staphylococcus aureus DSMZ 346 and Staphylococcus epidermidis DSMZ 20041. But also the other fusion proteins show antimicrobial activity against the two tested bacterial strains.

TABLE-US-00008 TABLE 8 Peptide Activity Activity stretch against against (N-terminal Staphylo- Staphylo- unless coccus coccus Fusion otherwise aureus epidermidis protein Enzyme part indicated) DSMZ 346 DSMZ 20041 SEQ ID LysK PK (SEQ ID + + NO: 118 (SEQ ID NO: 59) NO: 13) SEQ ID Lysostaphin PK (SEQ ID +++ +++ NO: 119 (SEQ ID NO: 60) NO: 13) SEQ ID Lysostaphin PK2 (SEQ ID +++ +++ NO: 120 (SEQ ID NO: 60) NO: 31) SEQ ID LysK PK (C-terminal) + + NO: 121 (SEQ ID NO: 59) (SEQ ID NO: 13) SEQ ID Lysostaphin PK (C-terminal) + + NO: 122 (SEQ ID NO: 60) (SEQ ID NO: 13) Abbreviations: +: 1 log; ++: 2-3 log; +++: 4 or more logs

EXAMPLE 5

Antimicrobial Activity of PA6-gp20 Enzyme Modified with the Hydrophobic Peptide Stretch Walmagh 1 The fusion protein PA6-gp20 with the N-terminal peptide stretch Walmagh 1 according to SEQ ID NO: 56 was produced as described in example 1. The antimicrobial activity of said fusion protein against Propionibacterium acnes DSMZ 1897 and Propionibacterium acnes DSMZ 16379 was tested by using the plating test described in example 2. The measured activity of the fusion protein is shown in Table 9.

[0138] The results presented in Table 9 show antimicrobial activity of the fusion protein against both bacterial strains of Propionibacterium acnes.

TABLE-US-00009 TABLE 9 Activity Activity Peptide against against stretch Propioni- Propioni- (N-terminal bacterium bacterium unless acnes acnes Fusion otherwise DSMZ DSMZ protein Enzyme part indicated) 1897 16379 SEQ ID PA6-gp20 Walmagh 1 ++ ++ NO: 124 (SEQ ID (SEQ ID NO: 61) NO: 56) Abbreviations: ++: 2-3 log;

[0139] The fusion proteins in Table 6 to 9 without any tag and linker were also tested with the activity assays described above. They all showed antimicrobial activity against the used bacterial strains in Table 6 to 9.

Sequence CWU 1

124125PRTUnknownamphipatic peptide Pleurocidin 1Gly Trp Gly Ser Phe Phe Lys Lys Ala Ala His Val Gly Lys His Val1 5 10 15Gly Lys Ala Ala Leu Thr His Tyr Leu 20 25231PRTUnknownamphipatic peptide Cecropin P1 2Ser Trp Leu Ser Lys Thr Ala Lys Lys Leu Glu Asn Ser Ala Lys Lys1 5 10 15Arg Ile Ser Glu Gly Ile Ala Ile Ala Ile Gln Gly Gly Pro Arg 20 25 30321PRTUnknownamphipatic peptide Buforin II 3Thr Arg Ser Ser Arg Ala Gly Leu Gln Phe Pro Val Gly Arg Val His1 5 10 15Arg Leu Leu Arg Lys 20423PRTUnknownamphipatic peptide Magainin 4Gly Ile Gly Lys Phe Leu His Ser Ala Lys Lys Phe Gly Lys Ala Phe1 5 10 15Val Gly Glu Ile Met Asn Ser 20537PRTUnknownamphipatic peptides Cathelidicine LL-37 5Leu Leu Gly Asp Phe Phe Arg Lys Ser Lys Glu Lys Ile Gly Lys Glu1 5 10 15Phe Lys Arg Ile Val Gln Arg Ile Lys Asp Phe Leu Arg Asn Leu Val 20 25 30Pro Arg Thr Glu Ser 35629PRTUnknownSMAP-29 6Arg Gly Leu Arg Arg Leu Gly Arg Lys Ile Ala His Gly Val Lys Lys1 5 10 15Tyr Gly Pro Thr Val Leu Arg Ile Ile Arg Ile Ala Gly 20 25713PRTUnknownIndolicidin 7Ile Leu Pro Trp Lys Trp Pro Trp Trp Pro Trp Arg Arg1 5 10818PRTUnknownProtegrin 8Arg Gly Gly Arg Leu Cys Tyr Cys Arg Arg Arg Phe Cys Val Cys Val1 5 10 15Gly Arg936PRTUnknownCecropin A (A.aegypti) 9Gly Gly Leu Lys Lys Leu Gly Lys Lys Leu Glu Gly Ala Gly Lys Arg1 5 10 15Val Phe Asn Ala Ala Glu Lys Ala Leu Pro Val Val Ala Gly Ala Lys 20 25 30Ala Leu Arg Lys 351040PRTUnknownCecropin A (D. melanogaster) 10Gly Trp Leu Lys Lys Ile Gly Lys Lys Ile Glu Arg Val Gly Gln His1 5 10 15Thr Arg Asp Ala Thr Ile Gln Gly Leu Gly Ile Pro Gln Gln Ala Ala 20 25 30Asn Val Ala Ala Thr Ala Arg Gly 35 401139PRTUnknownSarcotoxin IA 11Gly Trp Leu Lys Lys Ile Gly Lys Lys Ile Glu Arg Val Gly Gln His1 5 10 15Thr Arg Asp Ala Thr Ile Gln Gly Leu Gly Ile Ala Gln Gln Ala Ala 20 25 30Asn Val Ala Ala Thr Ala Arg 35125PRTUnknownSynthetic Peptide 12Phe Phe Val Ala Pro1 5139PRTUnknowncationic peptides 13Lys Arg Lys Lys Arg Lys Lys Arg Lys1 51431PRTUnknowncationic peptides 14Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg1 5 10 15Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg Lys Lys Arg Lys 20 25 3015506PRTUnknownputative lysin [Staphylococcus phage K] 15Met Gly Ser Lys Arg Lys Lys Arg Lys Lys Arg Lys Ala Lys Thr Gln1 5 10 15Ala Glu Ile Asn Lys Arg Leu Asp Ala Tyr Ala Lys Gly Thr Val Asp 20 25 30Ser Pro Tyr Arg Val Lys Lys Ala Thr Ser Tyr Asp Pro Ser Phe Gly 35 40 45Val Met Glu Ala Gly Ala Ile Asp Ala Asp Gly Tyr Tyr His Ala Gln 50 55 60Cys Gln Asp Leu Ile Thr Asp Tyr Val Leu Trp Leu Thr Asp Asn Lys65 70 75 80Val Arg Thr Trp Gly Asn Ala Lys Asp Gln Ile Lys Gln Ser Tyr Gly 85 90 95Thr Gly Phe Lys Ile His Glu Asn Lys Pro Ser Thr Val Pro Lys Lys 100 105 110Gly Trp Ile Ala Val Phe Thr Ser Gly Ser Tyr Glu Gln Trp Gly His 115 120 125Ile Gly Ile Val Tyr Asp Gly Gly Asn Thr Ser Thr Phe Thr Ile Leu 130 135 140Glu Gln Asn Trp Asn Gly Tyr Ala Asn Lys Lys Pro Thr Lys Arg Val145 150 155 160Asp Asn Tyr Tyr Gly Leu Thr His Phe Ile Glu Ile Pro Val Lys Ala 165 170 175Gly Thr Thr Val Lys Lys Glu Thr Ala Lys Lys Ser Ala Ser Lys Thr 180 185 190Pro Ala Pro Lys Lys Lys Ala Thr Leu Lys Val Ser Lys Asn His Ile 195 200 205Asn Tyr Thr Met Asp Lys Arg Gly Lys Lys Pro Glu Gly Met Val Ile 210 215 220His Asn Asp Ala Gly Arg Ser Ser Gly Gln Gln Tyr Glu Asn Ser Leu225 230 235 240Ala Asn Ala Gly Tyr Ala Arg Tyr Ala Asn Gly Ile Ala His Tyr Tyr 245 250 255Gly Ser Glu Gly Tyr Val Trp Glu Ala Ile Asp Ala Lys Asn Gln Ile 260 265 270Ala Trp His Thr Gly Asp Gly Thr Gly Ala Asn Ser Gly Asn Phe Arg 275 280 285Phe Ala Gly Ile Glu Val Cys Gln Ser Met Ser Ala Ser Asp Ala Gln 290 295 300Phe Leu Lys Asn Glu Gln Ala Val Phe Gln Phe Thr Ala Glu Lys Phe305 310 315 320Lys Glu Trp Gly Leu Thr Pro Asn Arg Lys Thr Val Arg Leu His Met 325 330 335Glu Phe Val Pro Thr Ala Cys Pro His Arg Ser Met Val Leu His Thr 340 345 350Gly Phe Asn Pro Val Thr Gln Gly Arg Pro Ser Gln Ala Ile Met Asn 355 360 365Lys Leu Lys Asp Tyr Phe Ile Lys Gln Ile Lys Asn Tyr Met Asp Lys 370 375 380Gly Thr Ser Ser Ser Thr Val Val Lys Asp Gly Lys Thr Ser Ser Ala385 390 395 400Ser Thr Pro Ala Thr Arg Pro Val Thr Gly Ser Trp Lys Lys Asn Gln 405 410 415Tyr Gly Thr Trp Tyr Lys Pro Glu Asn Ala Thr Phe Val Asn Gly Asn 420 425 430Gln Pro Ile Val Thr Arg Ile Gly Ser Pro Phe Leu Asn Ala Pro Val 435 440 445Gly Gly Asn Leu Pro Ala Gly Ala Thr Ile Val Tyr Asp Glu Val Cys 450 455 460Ile Gln Ala Gly His Ile Trp Ile Gly Tyr Asn Ala Tyr Asn Gly Asn465 470 475 480Arg Val Tyr Cys Pro Val Arg Thr Cys Gln Gly Val Pro Pro Asn Gln 485 490 495Ile Pro Gly Val Ala Trp Gly Val Phe Lys 500 50516528PRTUnknownPutative Lysin Staphylococcus phage K 16Met Gly Ser Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Ser Lys Arg1 5 10 15Lys Lys Arg Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg Lys Lys 20 25 30Arg Lys Ala Lys Thr Gln Ala Glu Ile Asn Lys Arg Leu Asp Ala Tyr 35 40 45Ala Lys Gly Thr Val Asp Ser Pro Tyr Arg Val Lys Lys Ala Thr Ser 50 55 60Tyr Asp Pro Ser Phe Gly Val Met Glu Ala Gly Ala Ile Asp Ala Asp65 70 75 80Gly Tyr Tyr His Ala Gln Cys Gln Asp Leu Ile Thr Asp Tyr Val Leu 85 90 95Trp Leu Thr Asp Asn Lys Val Arg Thr Trp Gly Asn Ala Lys Asp Gln 100 105 110Ile Lys Gln Ser Tyr Gly Thr Gly Phe Lys Ile His Glu Asn Lys Pro 115 120 125Ser Thr Val Pro Lys Lys Gly Trp Ile Ala Val Phe Thr Ser Gly Ser 130 135 140Tyr Glu Gln Trp Gly His Ile Gly Ile Val Tyr Asp Gly Gly Asn Thr145 150 155 160Ser Thr Phe Thr Ile Leu Glu Gln Asn Trp Asn Gly Tyr Ala Asn Lys 165 170 175Lys Pro Thr Lys Arg Val Asp Asn Tyr Tyr Gly Leu Thr His Phe Ile 180 185 190Glu Ile Pro Val Lys Ala Gly Thr Thr Val Lys Lys Glu Thr Ala Lys 195 200 205Lys Ser Ala Ser Lys Thr Pro Ala Pro Lys Lys Lys Ala Thr Leu Lys 210 215 220Val Ser Lys Asn His Ile Asn Tyr Thr Met Asp Lys Arg Gly Lys Lys225 230 235 240Pro Glu Gly Met Val Ile His Asn Asp Ala Gly Arg Ser Ser Gly Gln 245 250 255Gln Tyr Glu Asn Ser Leu Ala Asn Ala Gly Tyr Ala Arg Tyr Ala Asn 260 265 270Gly Ile Ala His Tyr Tyr Gly Ser Glu Gly Tyr Val Trp Glu Ala Ile 275 280 285Asp Ala Lys Asn Gln Ile Ala Trp His Thr Gly Asp Gly Thr Gly Ala 290 295 300Asn Ser Gly Asn Phe Arg Phe Ala Gly Ile Glu Val Cys Gln Ser Met305 310 315 320Ser Ala Ser Asp Ala Gln Phe Leu Lys Asn Glu Gln Ala Val Phe Gln 325 330 335Phe Thr Ala Glu Lys Phe Lys Glu Trp Gly Leu Thr Pro Asn Arg Lys 340 345 350Thr Val Arg Leu His Met Glu Phe Val Pro Thr Ala Cys Pro His Arg 355 360 365Ser Met Val Leu His Thr Gly Phe Asn Pro Val Thr Gln Gly Arg Pro 370 375 380Ser Gln Ala Ile Met Asn Lys Leu Lys Asp Tyr Phe Ile Lys Gln Ile385 390 395 400Lys Asn Tyr Met Asp Lys Gly Thr Ser Ser Ser Thr Val Val Lys Asp 405 410 415Gly Lys Thr Ser Ser Ala Ser Thr Pro Ala Thr Arg Pro Val Thr Gly 420 425 430Ser Trp Lys Lys Asn Gln Tyr Gly Thr Trp Tyr Lys Pro Glu Asn Ala 435 440 445Thr Phe Val Asn Gly Asn Gln Pro Ile Val Thr Arg Ile Gly Ser Pro 450 455 460Phe Leu Asn Ala Pro Val Gly Gly Asn Leu Pro Ala Gly Ala Thr Ile465 470 475 480Val Tyr Asp Glu Val Cys Ile Gln Ala Gly His Ile Trp Ile Gly Tyr 485 490 495Asn Ala Tyr Asn Gly Asn Arg Val Tyr Cys Pro Val Arg Thr Cys Gln 500 505 510Gly Val Pro Pro Asn Gln Ile Pro Gly Val Ala Trp Gly Val Phe Lys 515 520 52517505PRTUnknownPutative Lysin Staphylococcus phage K 17Met Ala Lys Thr Gln Ala Glu Ile Asn Lys Arg Leu Asp Ala Tyr Ala1 5 10 15Lys Gly Thr Val Asp Ser Pro Tyr Arg Val Lys Lys Ala Thr Ser Tyr 20 25 30Asp Pro Ser Phe Gly Val Met Glu Ala Gly Ala Ile Asp Ala Asp Gly 35 40 45Tyr Tyr His Ala Gln Cys Gln Asp Leu Ile Thr Asp Tyr Val Leu Trp 50 55 60Leu Thr Asp Asn Lys Val Arg Thr Trp Gly Asn Ala Lys Asp Gln Ile65 70 75 80Lys Gln Ser Tyr Gly Thr Gly Phe Lys Ile His Glu Asn Lys Pro Ser 85 90 95Thr Val Pro Lys Lys Gly Trp Ile Ala Val Phe Thr Ser Gly Ser Tyr 100 105 110Glu Gln Trp Gly His Ile Gly Ile Val Tyr Asp Gly Gly Asn Thr Ser 115 120 125Thr Phe Thr Ile Leu Glu Gln Asn Trp Asn Gly Tyr Ala Asn Lys Lys 130 135 140Pro Thr Lys Arg Val Asp Asn Tyr Tyr Gly Leu Thr His Phe Ile Glu145 150 155 160Ile Pro Val Lys Ala Gly Thr Thr Val Lys Lys Glu Thr Ala Lys Lys 165 170 175Ser Ala Ser Lys Thr Pro Ala Pro Lys Lys Lys Ala Thr Leu Lys Val 180 185 190Ser Lys Asn His Ile Asn Tyr Thr Met Asp Lys Arg Gly Lys Lys Pro 195 200 205Glu Gly Met Val Ile His Asn Asp Ala Gly Arg Ser Ser Gly Gln Gln 210 215 220Tyr Glu Asn Ser Leu Ala Asn Ala Gly Tyr Ala Arg Tyr Ala Asn Gly225 230 235 240Ile Ala His Tyr Tyr Gly Ser Glu Gly Tyr Val Trp Glu Ala Ile Asp 245 250 255Ala Lys Asn Gln Ile Ala Trp His Thr Gly Asp Gly Thr Gly Ala Asn 260 265 270Ser Gly Asn Phe Arg Phe Ala Gly Ile Glu Val Cys Gln Ser Met Ser 275 280 285Ala Ser Asp Ala Gln Phe Leu Lys Asn Glu Gln Ala Val Phe Gln Phe 290 295 300Thr Ala Glu Lys Phe Lys Glu Trp Gly Leu Thr Pro Asn Arg Lys Thr305 310 315 320Val Arg Leu His Met Glu Phe Val Pro Thr Ala Cys Pro His Arg Ser 325 330 335Met Val Leu His Thr Gly Phe Asn Pro Val Thr Gln Gly Arg Pro Ser 340 345 350Gln Ala Ile Met Asn Lys Leu Lys Asp Tyr Phe Ile Lys Gln Ile Lys 355 360 365Asn Tyr Met Asp Lys Gly Thr Ser Ser Ser Thr Val Val Lys Asp Gly 370 375 380Lys Thr Ser Ser Ala Ser Thr Pro Ala Thr Arg Pro Val Thr Gly Ser385 390 395 400Trp Lys Lys Asn Gln Tyr Gly Thr Trp Tyr Lys Pro Glu Asn Ala Thr 405 410 415Phe Val Asn Gly Asn Gln Pro Ile Val Thr Arg Ile Gly Ser Pro Phe 420 425 430Leu Asn Ala Pro Val Gly Gly Asn Leu Pro Ala Gly Ala Thr Ile Val 435 440 445Tyr Asp Glu Val Cys Ile Gln Ala Gly His Ile Trp Ile Gly Tyr Asn 450 455 460Ala Tyr Asn Gly Asn Arg Val Tyr Cys Pro Val Arg Thr Cys Gln Gly465 470 475 480Val Pro Pro Asn Gln Ile Pro Gly Val Ala Trp Gly Val Phe Lys Ser 485 490 495Lys Arg Lys Lys Arg Lys Lys Arg Lys 500 50518527PRTUnknownPutative Lysin Staphylococcus phage K 18Met Ala Lys Thr Gln Ala Glu Ile Asn Lys Arg Leu Asp Ala Tyr Ala1 5 10 15Lys Gly Thr Val Asp Ser Pro Tyr Arg Val Lys Lys Ala Thr Ser Tyr 20 25 30Asp Pro Ser Phe Gly Val Met Glu Ala Gly Ala Ile Asp Ala Asp Gly 35 40 45Tyr Tyr His Ala Gln Cys Gln Asp Leu Ile Thr Asp Tyr Val Leu Trp 50 55 60Leu Thr Asp Asn Lys Val Arg Thr Trp Gly Asn Ala Lys Asp Gln Ile65 70 75 80Lys Gln Ser Tyr Gly Thr Gly Phe Lys Ile His Glu Asn Lys Pro Ser 85 90 95Thr Val Pro Lys Lys Gly Trp Ile Ala Val Phe Thr Ser Gly Ser Tyr 100 105 110Glu Gln Trp Gly His Ile Gly Ile Val Tyr Asp Gly Gly Asn Thr Ser 115 120 125Thr Phe Thr Ile Leu Glu Gln Asn Trp Asn Gly Tyr Ala Asn Lys Lys 130 135 140Pro Thr Lys Arg Val Asp Asn Tyr Tyr Gly Leu Thr His Phe Ile Glu145 150 155 160Ile Pro Val Lys Ala Gly Thr Thr Val Lys Lys Glu Thr Ala Lys Lys 165 170 175Ser Ala Ser Lys Thr Pro Ala Pro Lys Lys Lys Ala Thr Leu Lys Val 180 185 190Ser Lys Asn His Ile Asn Tyr Thr Met Asp Lys Arg Gly Lys Lys Pro 195 200 205Glu Gly Met Val Ile His Asn Asp Ala Gly Arg Ser Ser Gly Gln Gln 210 215 220Tyr Glu Asn Ser Leu Ala Asn Ala Gly Tyr Ala Arg Tyr Ala Asn Gly225 230 235 240Ile Ala His Tyr Tyr Gly Ser Glu Gly Tyr Val Trp Glu Ala Ile Asp 245 250 255Ala Lys Asn Gln Ile Ala Trp His Thr Gly Asp Gly Thr Gly Ala Asn 260 265 270Ser Gly Asn Phe Arg Phe Ala Gly Ile Glu Val Cys Gln Ser Met Ser 275 280 285Ala Ser Asp Ala Gln Phe Leu Lys Asn Glu Gln Ala Val Phe Gln Phe 290 295 300Thr Ala Glu Lys Phe Lys Glu Trp Gly Leu Thr Pro Asn Arg Lys Thr305 310 315 320Val Arg Leu His Met Glu Phe Val Pro Thr Ala Cys Pro His Arg Ser 325 330 335Met Val Leu His Thr Gly Phe Asn Pro Val Thr Gln Gly Arg Pro Ser 340 345 350Gln Ala Ile Met Asn Lys Leu Lys Asp Tyr Phe Ile Lys Gln Ile Lys 355 360 365Asn Tyr Met Asp Lys Gly Thr Ser Ser Ser Thr Val Val Lys Asp Gly 370 375 380Lys Thr Ser Ser Ala Ser Thr Pro Ala Thr Arg Pro Val Thr Gly Ser385 390 395 400Trp Lys Lys Asn Gln Tyr Gly Thr Trp Tyr Lys Pro Glu Asn Ala Thr 405 410 415Phe Val Asn Gly Asn Gln Pro Ile Val Thr Arg Ile Gly Ser Pro Phe 420 425 430Leu Asn Ala Pro Val Gly Gly Asn Leu Pro Ala Gly Ala Thr Ile Val 435 440 445Tyr Asp Glu Val Cys Ile Gln Ala Gly His Ile Trp Ile Gly Tyr Asn 450 455 460Ala Tyr Asn Gly Asn Arg Val Tyr Cys Pro Val Arg Thr Cys Gln Gly465 470 475 480Val Pro Pro Asn Gln Ile Pro

Gly Val Ala Trp Gly Val Phe Lys Ser 485 490 495Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg 500 505 510Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg Lys Lys Arg Lys 515 520 52519255PRTUnknownLysostaphin 19Met Gly Ser Lys Arg Lys Lys Arg Lys Lys Arg Lys His Glu His Ser1 5 10 15Ala Gln Trp Leu Asn Asn Tyr Lys Lys Gly Tyr Gly Tyr Gly Pro Tyr 20 25 30Pro Leu Gly Ile Asn Gly Gly Met His Tyr Gly Val Asp Phe Phe Met 35 40 45Asn Ile Gly Thr Pro Val Lys Ala Ile Ser Ser Gly Lys Ile Val Glu 50 55 60Ala Gly Trp Ser Asn Tyr Gly Gly Gly Asn Gln Ile Gly Leu Ile Glu65 70 75 80Asn Asp Gly Val His Arg Gln Trp Tyr Met His Leu Ser Lys Tyr Asn 85 90 95Val Lys Val Gly Asp Tyr Val Lys Ala Gly Gln Ile Ile Gly Trp Ser 100 105 110Gly Ser Thr Gly Tyr Ser Thr Ala Pro His Leu His Phe Gln Arg Met 115 120 125Val Asn Ser Phe Ser Asn Ser Thr Ala Gln Asp Pro Met Pro Phe Leu 130 135 140Lys Ser Ala Gly Tyr Gly Lys Ala Gly Gly Thr Val Thr Pro Thr Pro145 150 155 160Asn Thr Gly Trp Lys Thr Asn Lys Tyr Gly Thr Leu Tyr Lys Ser Glu 165 170 175Ser Ala Ser Phe Thr Pro Asn Thr Asp Ile Ile Thr Arg Thr Thr Gly 180 185 190Pro Phe Arg Ser Met Pro Gln Ser Gly Val Leu Lys Ala Gly Gln Thr 195 200 205Ile His Tyr Asp Glu Val Met Lys Gln Asp Gly His Val Trp Val Gly 210 215 220Tyr Thr Gly Asn Ser Gly Gln Arg Ile Tyr Leu Pro Val Arg Thr Trp225 230 235 240Asn Lys Ser Thr Asn Thr Leu Gly Val Leu Trp Gly Thr Ile Lys 245 250 25520277PRTUnknownLysostaphin 20Met Gly Ser Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Ser Lys Arg1 5 10 15Lys Lys Arg Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg Lys Lys 20 25 30Arg Lys His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys Lys Gly 35 40 45Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met His Tyr 50 55 60Gly Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala Ile Ser65 70 75 80Ser Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly Gly Asn 85 90 95Gln Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp Tyr Met 100 105 110His Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys Ala Gly 115 120 125Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala Pro His 130 135 140Leu His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr Ala Gln145 150 155 160Asp Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Lys Ala Gly Gly 165 170 175Thr Val Thr Pro Thr Pro Asn Thr Gly Trp Lys Thr Asn Lys Tyr Gly 180 185 190Thr Leu Tyr Lys Ser Glu Ser Ala Ser Phe Thr Pro Asn Thr Asp Ile 195 200 205Ile Thr Arg Thr Thr Gly Pro Phe Arg Ser Met Pro Gln Ser Gly Val 210 215 220Leu Lys Ala Gly Gln Thr Ile His Tyr Asp Glu Val Met Lys Gln Asp225 230 235 240Gly His Val Trp Val Gly Tyr Thr Gly Asn Ser Gly Gln Arg Ile Tyr 245 250 255Leu Pro Val Arg Thr Trp Asn Lys Ser Thr Asn Thr Leu Gly Val Leu 260 265 270Trp Gly Thr Ile Lys 27521254PRTUnknownLysostaphin 21Met His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys Lys Gly Tyr1 5 10 15Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met His Tyr Gly 20 25 30Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala Ile Ser Ser 35 40 45Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly Gly Asn Gln 50 55 60Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp Tyr Met His65 70 75 80Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys Ala Gly Gln 85 90 95Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala Pro His Leu 100 105 110His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr Ala Gln Asp 115 120 125Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Lys Ala Gly Gly Thr 130 135 140Val Thr Pro Thr Pro Asn Thr Gly Trp Lys Thr Asn Lys Tyr Gly Thr145 150 155 160Leu Tyr Lys Ser Glu Ser Ala Ser Phe Thr Pro Asn Thr Asp Ile Ile 165 170 175Thr Arg Thr Thr Gly Pro Phe Arg Ser Met Pro Gln Ser Gly Val Leu 180 185 190Lys Ala Gly Gln Thr Ile His Tyr Asp Glu Val Met Lys Gln Asp Gly 195 200 205His Val Trp Val Gly Tyr Thr Gly Asn Ser Gly Gln Arg Ile Tyr Leu 210 215 220Pro Val Arg Thr Trp Asn Lys Ser Thr Asn Thr Leu Gly Val Leu Trp225 230 235 240Gly Thr Ile Lys Ser Lys Arg Lys Lys Arg Lys Lys Arg Lys 245 25022276PRTUnknownLysostaphin 22Met His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys Lys Gly Tyr1 5 10 15Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met His Tyr Gly 20 25 30Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala Ile Ser Ser 35 40 45Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly Gly Asn Gln 50 55 60Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp Tyr Met His65 70 75 80Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys Ala Gly Gln 85 90 95Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala Pro His Leu 100 105 110His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr Ala Gln Asp 115 120 125Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Lys Ala Gly Gly Thr 130 135 140Val Thr Pro Thr Pro Asn Thr Gly Trp Lys Thr Asn Lys Tyr Gly Thr145 150 155 160Leu Tyr Lys Ser Glu Ser Ala Ser Phe Thr Pro Asn Thr Asp Ile Ile 165 170 175Thr Arg Thr Thr Gly Pro Phe Arg Ser Met Pro Gln Ser Gly Val Leu 180 185 190Lys Ala Gly Gln Thr Ile His Tyr Asp Glu Val Met Lys Gln Asp Gly 195 200 205His Val Trp Val Gly Tyr Thr Gly Asn Ser Gly Gln Arg Ile Tyr Leu 210 215 220Pro Val Arg Thr Trp Asn Lys Ser Thr Asn Thr Leu Gly Val Leu Trp225 230 235 240Gly Thr Ile Lys Ser Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Ser 245 250 255Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg 260 265 270Lys Lys Arg Lys 2752339PRTUnknownBuforin I 23Ala Gly Arg Gly Lys Gln Gly Gly Lys Val Arg Ala Lys Ala Lys Thr1 5 10 15Arg Ser Ser Arg Ala Gly Leu Gln Phe Pro Val Gly Arg Val His Arg 20 25 30Leu Leu Arg Lys Gly Asn Tyr 35246PRTUnknownpeptide stretch 24Lys Arg Lys Lys Arg Lys1 5259PRTUnknownpeptide stretch 25Arg Arg Arg Arg Arg Arg Arg Arg Arg1 5268PRTUnknownpeptide stretch 26Lys Lys Lys Lys Lys Lys Lys Lys1 52710PRTUnknownpeptide stretch 27Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys1 5 102812PRTUnknownpeptide stretch 28Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys1 5 102914PRTUnknownpeptide stretch 29Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg1 5 103016PRTUnknownpeptide stretch 30Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys1 5 10 153118PRTUnknownpeptide stretch 31Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys1 5 10 15Arg Lys3219PRTUnknownpeptide stretch 32Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys1 5 10 15Arg Lys Lys3319PRTUnknownpeptide stretch 33Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg1 5 10 15Arg Arg Arg3419PRTUnknownpeptide stretch 34Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys1 5 10 15Lys Lys Lys3520PRTUnknownpeptide stretch 35Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg1 5 10 15Lys Lys Arg Lys 203621PRTUnknownpeptide stretch 36Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg1 5 10 15Lys Lys Arg Lys Lys 203721PRTUnknownpeptide stretch 37Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys1 5 10 15Arg Lys Lys Arg Lys 203822PRTUnknownpeptide stretch 38Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Gly Ser Gly Lys Arg Lys1 5 10 15Lys Arg Lys Lys Arg Lys 203924PRTUnknownpeptide stretch 39Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Gly Ser Gly Ser Gly Lys1 5 10 15Arg Lys Lys Arg Lys Lys Arg Lys 204025PRTUnknownpeptide stretch 40Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys1 5 10 15Arg Lys Lys Arg Lys Lys Arg Lys Lys 20 254131PRTUnknownpeptide stretch 41Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg1 5 10 15Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg Lys Lys Arg Lys 20 25 304238PRTUnknownpeptide stretch 42Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Gly Ser Gly Ser Gly Lys1 5 10 15Arg Lys Lys Arg Lys Lys Arg Lys Gly Ser Gly Ser Gly Lys Arg Lys 20 25 30Lys Arg Lys Lys Arg Lys 354339PRTUnknownpeptide stretch 43Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys1 5 10 15Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg 20 25 30Lys Lys Arg Lys Lys Arg Lys 354442PRTUnknownpeptide stretch 44Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg1 5 10 15Lys Lys Arg Lys Arg Ser Lys Arg Lys Lys Arg Lys Lys Arg Lys Arg 20 25 30Ser Lys Arg Lys Lys Arg Lys Lys Arg Lys 35 40455PRTUnknownmotif for polypeptide stretches, wherein X is any other amino acid than lysine, arginine and histidine 45Lys Arg Xaa Lys Arg1 5465PRTUnknownmotif for polypeptide stretches 46Lys Arg Ser Lys Arg1 5475PRTUnknownmotif for polypeptide stretches 47Lys Arg Gly Ser Gly1 54822PRTUnknownNigrocine 2 48Gly Leu Leu Ser Lys Val Leu Gly Val Gly Lys Lys Val Leu Cys Gly1 5 10 15Val Ser Gly Leu Val Cys 204924PRTUnknownAscaphine 5 49Gly Ile Lys Asp Trp Ile Lys Gly Ala Ala Lys Lys Leu Ile Lys Thr1 5 10 15Val Ala Ser His Ile Ala Asn Gln 205017PRTUnknownApidaecine 50Ala Asn Arg Pro Val Tyr Ile Pro Pro Pro Arg Pro Pro His Pro Arg1 5 10 15Leu5124PRTUnknownPseudin 1 51Gly Leu Asn Thr Leu Lys Lys Val Phe Gln Gly Leu His Glu Ala Ile1 5 10 15Lys Leu Ile Asn Asn His Val Gln 205218PRTUnknownRanalexin 52Phe Leu Gly Gly Leu Ile Val Pro Ala Met Ile Cys Ala Val Thr Lys1 5 10 15Lys Cys5326PRTUnknownMelittin 53Gly Ile Gly Ala Val Leu Lys Val Leu Thr Thr Gly Leu Pro Ala Leu1 5 10 15Ile Ser Trp Ile Lys Arg Lys Arg Gln Gln 20 255434PRTUnknownSushi 1 peptide 54Gly Phe Lys Leu Lys Gly Met Ala Arg Ile Ser Cys Leu Pro Asn Gly1 5 10 15Gln Trp Ser Asn Phe Pro Pro Lys Cys Ile Arg Glu Cys Ala Met Val 20 25 30Ser Ser5527PRTUnknownWLBU2-Variant 55Lys Arg Trp Val Lys Arg Val Lys Arg Val Lys Arg Trp Val Lys Arg1 5 10 15Val Val Arg Val Val Lys Arg Trp Val Lys Arg 20 255618PRTUnknownWalmagh1 56Gly Phe Phe Ile Pro Ala Val Ile Leu Pro Ser Ile Ala Phe Leu Ile1 5 10 15Val Pro57339PRTUnknownCpl-1 57Met Val Lys Lys Asn Asp Leu Phe Val Asp Val Ser Ser His Asn Gly1 5 10 15Tyr Asp Ile Thr Gly Ile Leu Glu Gln Met Gly Thr Thr Asn Thr Ile 20 25 30Ile Lys Ile Ser Glu Ser Thr Thr Tyr Leu Asn Pro Cys Leu Ser Ala 35 40 45Gln Val Glu Gln Ser Asn Pro Ile Gly Phe Tyr His Phe Ala Arg Phe 50 55 60Gly Gly Asp Val Ala Glu Ala Glu Arg Glu Ala Gln Phe Phe Leu Asp65 70 75 80Asn Val Pro Met Gln Val Lys Tyr Leu Val Leu Asp Tyr Glu Asp Asp 85 90 95Pro Ser Gly Asp Ala Gln Ala Asn Thr Asn Ala Cys Leu Arg Phe Met 100 105 110Gln Met Ile Ala Asp Ala Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys 115 120 125Pro Phe Thr His Asp Asn Val Asp Tyr Gln Gln Ile Leu Ala Gln Phe 130 135 140Pro Asn Ser Leu Trp Ile Ala Gly Tyr Gly Leu Asn Asp Gly Thr Ala145 150 155 160Asn Phe Glu Tyr Phe Pro Ser Met Asp Gly Ile Arg Trp Trp Gln Tyr 165 170 175Ser Ser Asn Pro Phe Asp Lys Asn Ile Val Leu Leu Asp Asp Glu Glu 180 185 190Asp Asp Lys Pro Lys Thr Ala Gly Thr Trp Lys Gln Asp Ser Lys Gly 195 200 205Trp Trp Phe Arg Arg Asn Asn Gly Ser Phe Pro Tyr Asn Lys Trp Glu 210 215 220Lys Ile Gly Gly Val Trp Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys Leu225 230 235 240Thr Ser Glu Trp Leu Lys Asp Asn Glu Lys Trp Tyr Tyr Leu Lys Asp 245 250 255Asn Gly Ala Met Ala Thr Gly Trp Val Leu Val Gly Ser Glu Trp Tyr 260 265 270Tyr Met Asp Asp Ser Gly Ala Met Val Thr Gly Trp Val Lys Tyr Lys 275 280 285Asn Asn Trp Tyr Tyr Met Thr Asn Glu Arg Gly Asn Met Val Ser Asn 290 295 300Glu Phe Ile Lys Ser Gly Lys Gly Trp Tyr Phe Met Asn Thr Asn Gly305 310 315 320Glu Leu Ala Asp Asn Pro Ser Phe Thr Lys Glu Pro Asp Gly Leu Ile 325 330 335Thr Val Ala58341PRTUnknownPly511 58Met Val Lys Tyr Thr Val Glu Asn Lys Ile Ile Ala Gly Leu Pro Lys1 5 10 15Gly Lys Leu Lys Gly Ala Asn Phe Val Ile Ala His Glu Thr Ala Asn 20 25 30Ser Lys Ser Thr Ile Asp Asn Glu Val Ser Tyr Met Thr Arg Asn Trp 35 40 45Lys Asn Ala Phe Val Thr His Phe Val Gly Gly Gly Gly Arg Val Val 50 55 60Gln Val Ala Asn Val Asn Tyr Val Ser Trp Gly Ala Gly Gln Tyr Ala65 70 75 80Asn Ser Tyr Ser Tyr Ala Gln Val Glu Leu Cys Arg Thr Ser Asn Ala 85 90 95Thr Thr Phe Lys Lys Asp Tyr Glu Val Tyr Cys Gln Leu Leu Val Asp 100 105 110Leu Ala Lys Lys Ala Gly Ile Pro Ile Thr Leu Asp Ser Gly Ser Lys 115 120 125Thr Ser Asp Lys Gly Ile Lys Ser His Lys Trp Val Ala Asp Lys Leu 130 135 140Gly Gly Thr Thr His Gln Asp Pro Tyr Ala Tyr Leu Ser Ser Trp Gly145 150 155 160Ile Ser Lys Ala Gln Phe Ala Ser Asp Leu

Ala Lys Val Ser Gly Gly 165 170 175Gly Asn Thr Gly Thr Ala Pro Ala Lys Pro Ser Thr Pro Ala Pro Lys 180 185 190Pro Ser Thr Pro Ser Thr Asn Leu Asp Lys Leu Gly Leu Val Asp Tyr 195 200 205Met Asn Ala Lys Lys Met Asp Ser Ser Tyr Ser Asn Arg Asp Lys Leu 210 215 220Ala Lys Gln Tyr Gly Ile Ala Asn Tyr Ser Gly Thr Ala Ser Gln Asn225 230 235 240Thr Thr Leu Leu Ser Lys Ile Lys Gly Gly Ala Pro Lys Pro Ser Thr 245 250 255Pro Ala Pro Lys Pro Ser Thr Ser Thr Ala Lys Lys Ile Tyr Phe Pro 260 265 270Pro Asn Lys Gly Asn Trp Ser Val Tyr Pro Thr Asn Lys Ala Pro Val 275 280 285Lys Ala Asn Ala Ile Gly Ala Ile Asn Pro Thr Lys Phe Gly Gly Leu 290 295 300Thr Tyr Thr Ile Gln Lys Asp Arg Gly Asn Gly Val Tyr Glu Ile Gln305 310 315 320Thr Asp Gln Phe Gly Arg Val Gln Val Tyr Gly Ala Pro Ser Thr Gly 325 330 335Ala Val Ile Lys Lys 34059495PRTUnknownLysK 59Met Ala Lys Thr Gln Ala Glu Ile Asn Lys Arg Leu Asp Ala Tyr Ala1 5 10 15Lys Gly Thr Val Asp Ser Pro Tyr Arg Val Lys Lys Ala Thr Ser Tyr 20 25 30Asp Pro Ser Phe Gly Val Met Glu Ala Gly Ala Ile Asp Ala Asp Gly 35 40 45Tyr Tyr His Ala Gln Cys Gln Asp Leu Ile Thr Asp Tyr Val Leu Trp 50 55 60Leu Thr Asp Asn Lys Val Arg Thr Trp Gly Asn Ala Lys Asp Gln Ile65 70 75 80Lys Gln Ser Tyr Gly Thr Gly Phe Lys Ile His Glu Asn Lys Pro Ser 85 90 95Thr Val Pro Lys Lys Gly Trp Ile Ala Val Phe Thr Ser Gly Ser Tyr 100 105 110Glu Gln Trp Gly His Ile Gly Ile Val Tyr Asp Gly Gly Asn Thr Ser 115 120 125Thr Phe Thr Ile Leu Glu Gln Asn Trp Asn Gly Tyr Ala Asn Lys Lys 130 135 140Pro Thr Lys Arg Val Asp Asn Tyr Tyr Gly Leu Thr His Phe Ile Glu145 150 155 160Ile Pro Val Lys Ala Gly Thr Thr Val Lys Lys Glu Thr Ala Lys Lys 165 170 175Ser Ala Ser Lys Thr Pro Ala Pro Lys Lys Lys Ala Thr Leu Lys Val 180 185 190Ser Lys Asn His Ile Asn Tyr Thr Met Asp Lys Arg Gly Lys Lys Pro 195 200 205Glu Gly Met Val Ile His Asn Asp Ala Gly Arg Ser Ser Gly Gln Gln 210 215 220Tyr Glu Asn Ser Leu Ala Asn Ala Gly Tyr Ala Arg Tyr Ala Asn Gly225 230 235 240Ile Ala His Tyr Tyr Gly Ser Glu Gly Tyr Val Trp Glu Ala Ile Asp 245 250 255Ala Lys Asn Gln Ile Ala Trp His Thr Gly Asp Gly Thr Gly Ala Asn 260 265 270Ser Gly Asn Phe Arg Phe Ala Gly Ile Glu Val Cys Gln Ser Met Ser 275 280 285Ala Ser Asp Ala Gln Phe Leu Lys Asn Glu Gln Ala Val Phe Gln Phe 290 295 300Thr Ala Glu Lys Phe Lys Glu Trp Gly Leu Thr Pro Asn Arg Lys Thr305 310 315 320Val Arg Leu His Met Glu Phe Val Pro Thr Ala Cys Pro His Arg Ser 325 330 335Met Val Leu His Thr Gly Phe Asn Pro Val Thr Gln Gly Arg Pro Ser 340 345 350Gln Ala Ile Met Asn Lys Leu Lys Asp Tyr Phe Ile Lys Gln Ile Lys 355 360 365Asn Tyr Met Asp Lys Gly Thr Ser Ser Ser Thr Val Val Lys Asp Gly 370 375 380Lys Thr Ser Ser Ala Ser Thr Pro Ala Thr Arg Pro Val Thr Gly Ser385 390 395 400Trp Lys Lys Asn Gln Tyr Gly Thr Trp Tyr Lys Pro Glu Asn Ala Thr 405 410 415Phe Val Asn Gly Asn Gln Pro Ile Val Thr Arg Ile Gly Ser Pro Phe 420 425 430Leu Asn Ala Pro Val Gly Gly Asn Leu Pro Ala Gly Ala Thr Ile Val 435 440 445Tyr Asp Glu Val Cys Ile Gln Ala Gly His Ile Trp Ile Gly Tyr Asn 450 455 460Ala Tyr Asn Gly Asn Arg Val Tyr Cys Pro Val Arg Thr Cys Gln Gly465 470 475 480Val Pro Pro Asn Gln Ile Pro Gly Val Ala Trp Gly Val Phe Lys 485 490 49560245PRTUnknownLysostaphin 60Met Ala His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys Lys Gly1 5 10 15Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met His Tyr 20 25 30Gly Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala Ile Ser 35 40 45Ser Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly Gly Asn 50 55 60Gln Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp Tyr Met65 70 75 80His Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys Ala Gly 85 90 95Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala Pro His 100 105 110Leu His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr Ala Gln 115 120 125Asp Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Lys Ala Gly Gly 130 135 140Thr Val Thr Pro Thr Pro Asn Thr Gly Trp Lys Thr Asn Lys Tyr Gly145 150 155 160Thr Leu Tyr Lys Ser Glu Ser Ala Ser Phe Thr Pro Asn Thr Asp Ile 165 170 175Ile Thr Arg Thr Thr Gly Pro Phe Arg Ser Met Pro Gln Ser Gly Val 180 185 190Leu Lys Ala Gly Gln Thr Ile His Tyr Asp Glu Val Met Lys Gln Asp 195 200 205Gly His Val Trp Val Gly Tyr Thr Gly Asn Ser Gly Gln Arg Ile Tyr 210 215 220Leu Pro Val Arg Thr Trp Asn Lys Ser Thr Asn Thr Leu Gly Val Leu225 230 235 240Trp Gly Thr Ile Lys 24561286PRTUnknownPA6-gp20 61Met Val Arg Tyr Ile Pro Ala Ala His His Ser Ala Gly Ser Asn Asn1 5 10 15Pro Val Asn Arg Val Val Ile His Ala Thr Cys Pro Asp Val Gly Phe 20 25 30Pro Ser Ala Ser Arg Lys Gly Arg Ala Val Ser Thr Ala Asn Tyr Phe 35 40 45Ala Ser Pro Ser Ser Gly Gly Ser Ala His Tyr Val Cys Asp Ile Gly 50 55 60Glu Thr Val Gln Cys Leu Ser Glu Ser Thr Ile Gly Trp His Ala Pro65 70 75 80Pro Asn Pro His Ser Leu Gly Ile Glu Ile Cys Ala Asp Gly Gly Ser 85 90 95His Ala Ser Phe Arg Val Pro Gly His Ala Tyr Thr Arg Glu Gln Trp 100 105 110Leu Asp Pro Gln Val Trp Pro Ala Val Glu Arg Ala Ala Val Leu Cys 115 120 125Arg Arg Leu Cys Asp Lys Tyr Asn Val Pro Lys Arg Lys Leu Ser Ala 130 135 140Ala Asp Leu Lys Ala Gly Arg Arg Gly Val Cys Gly His Val Asp Val145 150 155 160Thr Asp Ala Trp His Gln Ser Asp His Asp Asp Pro Gly Pro Trp Phe 165 170 175Pro Trp Asp Lys Phe Met Ala Val Val Asn Gly Gly Ser Gly Asp Ser 180 185 190Gly Glu Leu Thr Val Ala Asp Val Lys Ala Leu His Asp Gln Ile Lys 195 200 205Gln Leu Ser Ala Gln Leu Thr Gly Ser Val Asn Lys Leu His His Asp 210 215 220Val Gly Val Val Gln Val Gln Asn Gly Asp Leu Gly Lys Arg Val Asp225 230 235 240Ala Leu Ser Trp Val Lys Asn Pro Val Thr Gly Lys Leu Trp Arg Thr 245 250 255Lys Asp Ala Leu Trp Ser Val Trp Tyr Tyr Val Leu Glu Cys Arg Ser 260 265 270Arg Leu Asp Arg Leu Glu Ser Ala Val Asn Asp Leu Lys Lys 275 280 285626PRTUnknowncationic peptide 62Lys Arg Lys Lys Arg Lys1 563362PRTUnknownAscaphine5-Cpl1 63Gly Ile Lys Asp Trp Ile Lys Gly Ala Ala Lys Lys Leu Ile Lys Thr1 5 10 15Val Ala Ser His Ile Ala Asn Gln Val Lys Lys Asn Asp Leu Phe Val 20 25 30Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln 35 40 45Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr 50 55 60Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile Gly65 70 75 80Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu Arg 85 90 95Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr Leu 100 105 110Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr 115 120 125Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr Lys 130 135 140Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp Tyr145 150 155 160Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr 165 170 175Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp 180 185 190Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile 195 200 205Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr 210 215 220Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser225 230 235 240Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe 245 250 255Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu 260 265 270Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp Val 275 280 285Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met Val 290 295 300Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu305 310 315 320Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp 325 330 335Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr 340 345 350Lys Glu Pro Asp Gly Leu Ile Thr Val Ala 355 36064355PRTUnknownApidaecine-Cpl1 64Ala Asn Arg Pro Val Tyr Ile Pro Pro Pro Arg Pro Pro His Pro Arg1 5 10 15Leu Val Lys Lys Asn Asp Leu Phe Val Asp Val Ser Ser His Asn Gly 20 25 30Tyr Asp Ile Thr Gly Ile Leu Glu Gln Met Gly Thr Thr Asn Thr Ile 35 40 45Ile Lys Ile Ser Glu Ser Thr Thr Tyr Leu Asn Pro Cys Leu Ser Ala 50 55 60Gln Val Glu Gln Ser Asn Pro Ile Gly Phe Tyr His Phe Ala Arg Phe65 70 75 80Gly Gly Asp Val Ala Glu Ala Glu Arg Glu Ala Gln Phe Phe Leu Asp 85 90 95Asn Val Pro Met Gln Val Lys Tyr Leu Val Leu Asp Tyr Glu Asp Asp 100 105 110Pro Ser Gly Asp Ala Gln Ala Asn Thr Asn Ala Cys Leu Arg Phe Met 115 120 125Gln Met Ile Ala Asp Ala Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys 130 135 140Pro Phe Thr His Asp Asn Val Asp Tyr Gln Gln Ile Leu Ala Gln Phe145 150 155 160Pro Asn Ser Leu Trp Ile Ala Gly Tyr Gly Leu Asn Asp Gly Thr Ala 165 170 175Asn Phe Glu Tyr Phe Pro Ser Met Asp Gly Ile Arg Trp Trp Gln Tyr 180 185 190Ser Ser Asn Pro Phe Asp Lys Asn Ile Val Leu Leu Asp Asp Glu Glu 195 200 205Asp Asp Lys Pro Lys Thr Ala Gly Thr Trp Lys Gln Asp Ser Lys Gly 210 215 220Trp Trp Phe Arg Arg Asn Asn Gly Ser Phe Pro Tyr Asn Lys Trp Glu225 230 235 240Lys Ile Gly Gly Val Trp Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys Leu 245 250 255Thr Ser Glu Trp Leu Lys Asp Asn Glu Lys Trp Tyr Tyr Leu Lys Asp 260 265 270Asn Gly Ala Met Ala Thr Gly Trp Val Leu Val Gly Ser Glu Trp Tyr 275 280 285Tyr Met Asp Asp Ser Gly Ala Met Val Thr Gly Trp Val Lys Tyr Lys 290 295 300Asn Asn Trp Tyr Tyr Met Thr Asn Glu Arg Gly Asn Met Val Ser Asn305 310 315 320Glu Phe Ile Lys Ser Gly Lys Gly Trp Tyr Phe Met Asn Thr Asn Gly 325 330 335Glu Leu Ala Asp Asn Pro Ser Phe Thr Lys Glu Pro Asp Gly Leu Ile 340 345 350Thr Val Ala 35565360PRTUnknownNigrocine2-Cpl1 65Gly Leu Leu Ser Lys Val Leu Gly Val Gly Lys Lys Val Leu Cys Gly1 5 10 15Val Ser Gly Leu Val Cys Val Lys Lys Asn Asp Leu Phe Val Asp Val 20 25 30Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln Met Gly 35 40 45Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr Leu Asn 50 55 60Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile Gly Phe Tyr65 70 75 80His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu Arg Glu Ala 85 90 95Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr Leu Val Leu 100 105 110Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr Asn Ala 115 120 125Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr Lys Pro Ile 130 135 140Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp Tyr Gln Gln145 150 155 160Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr Gly Leu 165 170 175Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp Gly Ile 180 185 190Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile Val Leu 195 200 205Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr Trp Lys 210 215 220Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser Phe Pro225 230 235 240Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe Asp Ser 245 250 255Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu Lys Trp 260 265 270Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp Val Leu Val 275 280 285Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met Val Thr Gly 290 295 300Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu Arg Gly305 310 315 320Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp Tyr Phe 325 330 335Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr Lys Glu 340 345 350Pro Asp Gly Leu Ile Thr Val Ala 355 36066362PRTUnknownPseudin1-Cpl1 66Gly Leu Asn Thr Leu Lys Lys Val Phe Gln Gly Leu His Glu Ala Ile1 5 10 15Lys Leu Ile Asn Asn His Val Gln Val Lys Lys Asn Asp Leu Phe Val 20 25 30Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln 35 40 45Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr 50 55 60Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile Gly65 70 75 80Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu Arg 85 90 95Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr Leu 100 105 110Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr 115 120 125Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr Lys 130 135 140Pro Ile

Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp Tyr145 150 155 160Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr 165 170 175Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp 180 185 190Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile 195 200 205Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr 210 215 220Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser225 230 235 240Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe 245 250 255Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu 260 265 270Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp Val 275 280 285Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met Val 290 295 300Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu305 310 315 320Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp 325 330 335Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr 340 345 350Lys Glu Pro Asp Gly Leu Ile Thr Val Ala 355 36067356PRTUnknownRanalexin-Cpl1 67Phe Leu Gly Gly Leu Ile Val Pro Ala Met Ile Cys Ala Val Thr Lys1 5 10 15Lys Cys Val Lys Lys Asn Asp Leu Phe Val Asp Val Ser Ser His Asn 20 25 30Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln Met Gly Thr Thr Asn Thr 35 40 45Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr Leu Asn Pro Cys Leu Ser 50 55 60Ala Gln Val Glu Gln Ser Asn Pro Ile Gly Phe Tyr His Phe Ala Arg65 70 75 80Phe Gly Gly Asp Val Ala Glu Ala Glu Arg Glu Ala Gln Phe Phe Leu 85 90 95Asp Asn Val Pro Met Gln Val Lys Tyr Leu Val Leu Asp Tyr Glu Asp 100 105 110Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr Asn Ala Cys Leu Arg Phe 115 120 125Met Gln Met Ile Ala Asp Ala Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr 130 135 140Lys Pro Phe Thr His Asp Asn Val Asp Tyr Gln Gln Ile Leu Ala Gln145 150 155 160Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr Gly Leu Asn Asp Gly Thr 165 170 175Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp Gly Ile Arg Trp Trp Gln 180 185 190Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile Val Leu Leu Asp Asp Glu 195 200 205Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr Trp Lys Gln Asp Ser Lys 210 215 220Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser Phe Pro Tyr Asn Lys Trp225 230 235 240Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys 245 250 255Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu Lys Trp Tyr Tyr Leu Lys 260 265 270Asp Asn Gly Ala Met Ala Thr Gly Trp Val Leu Val Gly Ser Glu Trp 275 280 285Tyr Tyr Met Asp Asp Ser Gly Ala Met Val Thr Gly Trp Val Lys Tyr 290 295 300Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu Arg Gly Asn Met Val Ser305 310 315 320Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp Tyr Phe Met Asn Thr Asn 325 330 335Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr Lys Glu Pro Asp Gly Leu 340 345 350Ile Thr Val Ala 35568365PRTUnknownWLBU2-Variant-Cpl1 68Lys Arg Trp Val Lys Arg Val Lys Arg Val Lys Arg Trp Val Lys Arg1 5 10 15Val Val Arg Val Val Lys Arg Trp Val Lys Arg Val Lys Lys Asn Asp 20 25 30Leu Phe Val Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile 35 40 45Leu Glu Gln Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser 50 55 60Thr Thr Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn65 70 75 80Pro Ile Gly Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu 85 90 95Ala Glu Arg Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val 100 105 110Lys Tyr Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln 115 120 125Ala Asn Thr Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala 130 135 140Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn145 150 155 160Val Asp Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile 165 170 175Ala Gly Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro 180 185 190Ser Met Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp 195 200 205Lys Asn Ile Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr 210 215 220Ala Gly Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn225 230 235 240Asn Gly Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp 245 250 255Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys 260 265 270Asp Asn Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr 275 280 285Gly Trp Val Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly 290 295 300Ala Met Val Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met305 310 315 320Thr Asn Glu Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly 325 330 335Lys Gly Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro 340 345 350Ser Phe Thr Lys Glu Pro Asp Gly Leu Ile Thr Val Ala 355 360 36569372PRTUnknownSushi1-Cpl1 69Gly Phe Lys Leu Lys Gly Met Ala Arg Ile Ser Cys Leu Pro Asn Gly1 5 10 15Gln Trp Ser Asn Phe Pro Pro Lys Cys Ile Arg Glu Cys Ala Met Val 20 25 30Ser Ser Val Lys Lys Asn Asp Leu Phe Val Asp Val Ser Ser His Asn 35 40 45Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln Met Gly Thr Thr Asn Thr 50 55 60Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr Leu Asn Pro Cys Leu Ser65 70 75 80Ala Gln Val Glu Gln Ser Asn Pro Ile Gly Phe Tyr His Phe Ala Arg 85 90 95Phe Gly Gly Asp Val Ala Glu Ala Glu Arg Glu Ala Gln Phe Phe Leu 100 105 110Asp Asn Val Pro Met Gln Val Lys Tyr Leu Val Leu Asp Tyr Glu Asp 115 120 125Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr Asn Ala Cys Leu Arg Phe 130 135 140Met Gln Met Ile Ala Asp Ala Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr145 150 155 160Lys Pro Phe Thr His Asp Asn Val Asp Tyr Gln Gln Ile Leu Ala Gln 165 170 175Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr Gly Leu Asn Asp Gly Thr 180 185 190Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp Gly Ile Arg Trp Trp Gln 195 200 205Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile Val Leu Leu Asp Asp Glu 210 215 220Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr Trp Lys Gln Asp Ser Lys225 230 235 240Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser Phe Pro Tyr Asn Lys Trp 245 250 255Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys 260 265 270Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu Lys Trp Tyr Tyr Leu Lys 275 280 285Asp Asn Gly Ala Met Ala Thr Gly Trp Val Leu Val Gly Ser Glu Trp 290 295 300Tyr Tyr Met Asp Asp Ser Gly Ala Met Val Thr Gly Trp Val Lys Tyr305 310 315 320Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu Arg Gly Asn Met Val Ser 325 330 335Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp Tyr Phe Met Asn Thr Asn 340 345 350Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr Lys Glu Pro Asp Gly Leu 355 360 365Ile Thr Val Ala 37070364PRTUnknownMelttin-Cpl1 70Gly Ile Gly Ala Val Leu Lys Val Leu Thr Thr Gly Leu Pro Ala Leu1 5 10 15Ile Ser Trp Ile Lys Arg Lys Arg Gln Gln Val Lys Lys Asn Asp Leu 20 25 30Phe Val Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu 35 40 45Glu Gln Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr 50 55 60Thr Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro65 70 75 80Ile Gly Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala 85 90 95Glu Arg Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys 100 105 110Tyr Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala 115 120 125Asn Thr Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly 130 135 140Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val145 150 155 160Asp Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala 165 170 175Gly Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser 180 185 190Met Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys 195 200 205Asn Ile Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala 210 215 220Gly Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn225 230 235 240Gly Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr 245 250 255Tyr Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp 260 265 270Asn Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly 275 280 285Trp Val Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala 290 295 300Met Val Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr305 310 315 320Asn Glu Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys 325 330 335Gly Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser 340 345 350Phe Thr Lys Glu Pro Asp Gly Leu Ile Thr Val Ala 355 36071375PRTUnknownLL-37-Cpl1 71Leu Leu Gly Asp Phe Phe Arg Lys Ser Lys Glu Lys Ile Gly Lys Glu1 5 10 15Phe Lys Arg Ile Val Gln Arg Ile Lys Asp Phe Leu Arg Asn Leu Val 20 25 30Pro Arg Thr Glu Ser Val Lys Lys Asn Asp Leu Phe Val Asp Val Ser 35 40 45Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln Met Gly Thr 50 55 60Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr Leu Asn Pro65 70 75 80Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile Gly Phe Tyr His 85 90 95Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu Arg Glu Ala Gln 100 105 110Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr Leu Val Leu Asp 115 120 125Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr Asn Ala Cys 130 135 140Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr Lys Pro Ile Tyr145 150 155 160Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp Tyr Gln Gln Ile 165 170 175Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr Gly Leu Asn 180 185 190Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp Gly Ile Arg 195 200 205Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile Val Leu Leu 210 215 220Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr Trp Lys Gln225 230 235 240Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser Phe Pro Tyr 245 250 255Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe Asp Ser Lys 260 265 270Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu Lys Trp Tyr 275 280 285Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp Val Leu Val Gly 290 295 300Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met Val Thr Gly Trp305 310 315 320Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu Arg Gly Asn 325 330 335Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp Tyr Phe Met 340 345 350Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr Lys Glu Pro 355 360 365Asp Gly Leu Ile Thr Val Ala 370 37572351PRTUnknownIndolicidin-Cpl1 72Ile Leu Pro Trp Lys Trp Pro Trp Trp Pro Trp Arg Arg Val Lys Lys1 5 10 15Asn Asp Leu Phe Val Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr 20 25 30Gly Ile Leu Glu Gln Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser 35 40 45Glu Ser Thr Thr Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln 50 55 60Ser Asn Pro Ile Gly Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val65 70 75 80Ala Glu Ala Glu Arg Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met 85 90 95Gln Val Lys Tyr Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp 100 105 110Ala Gln Ala Asn Thr Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala 115 120 125Asp Ala Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His 130 135 140Asp Asn Val Asp Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu145 150 155 160Trp Ile Ala Gly Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr 165 170 175Phe Pro Ser Met Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro 180 185 190Phe Asp Lys Asn Ile Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro 195 200 205Lys Thr Ala Gly Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg 210 215 220Arg Asn Asn Gly Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly225 230 235 240Val Trp Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp 245 250 255Leu Lys Asp Asn Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met 260 265 270Ala Thr Gly Trp Val Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp 275 280 285Ser Gly Ala Met Val Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr 290 295 300Tyr Met Thr Asn Glu Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys305 310 315 320Ser Gly Lys Gly Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp 325 330 335Asn Pro Ser Phe Thr Lys Glu Pro Asp Gly Leu Ile Thr Val Ala 340 345 35073367PRTUnknownSMAP-29-Cpl1 73Arg Gly Leu Arg Arg Leu Gly Arg Lys Ile Ala His Gly Val Lys Lys1 5 10 15Tyr Gly Pro Thr Val Leu Arg Ile Ile Arg Ile Ala Gly Val Lys Lys 20 25 30Asn Asp Leu Phe Val Asp Val Ser Ser His Asn Gly Tyr

Asp Ile Thr 35 40 45Gly Ile Leu Glu Gln Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser 50 55 60Glu Ser Thr Thr Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln65 70 75 80Ser Asn Pro Ile Gly Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val 85 90 95Ala Glu Ala Glu Arg Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met 100 105 110Gln Val Lys Tyr Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp 115 120 125Ala Gln Ala Asn Thr Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala 130 135 140Asp Ala Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His145 150 155 160Asp Asn Val Asp Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu 165 170 175Trp Ile Ala Gly Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr 180 185 190Phe Pro Ser Met Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro 195 200 205Phe Asp Lys Asn Ile Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro 210 215 220Lys Thr Ala Gly Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg225 230 235 240Arg Asn Asn Gly Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly 245 250 255Val Trp Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp 260 265 270Leu Lys Asp Asn Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met 275 280 285Ala Thr Gly Trp Val Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp 290 295 300Ser Gly Ala Met Val Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr305 310 315 320Tyr Met Thr Asn Glu Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys 325 330 335Ser Gly Lys Gly Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp 340 345 350Asn Pro Ser Phe Thr Lys Glu Pro Asp Gly Leu Ile Thr Val Ala 355 360 36574356PRTUnknownProtegrin-Cpl1 74Arg Gly Gly Arg Leu Cys Tyr Cys Arg Arg Arg Phe Cys Val Cys Val1 5 10 15Gly Arg Val Lys Lys Asn Asp Leu Phe Val Asp Val Ser Ser His Asn 20 25 30Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln Met Gly Thr Thr Asn Thr 35 40 45Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr Leu Asn Pro Cys Leu Ser 50 55 60Ala Gln Val Glu Gln Ser Asn Pro Ile Gly Phe Tyr His Phe Ala Arg65 70 75 80Phe Gly Gly Asp Val Ala Glu Ala Glu Arg Glu Ala Gln Phe Phe Leu 85 90 95Asp Asn Val Pro Met Gln Val Lys Tyr Leu Val Leu Asp Tyr Glu Asp 100 105 110Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr Asn Ala Cys Leu Arg Phe 115 120 125Met Gln Met Ile Ala Asp Ala Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr 130 135 140Lys Pro Phe Thr His Asp Asn Val Asp Tyr Gln Gln Ile Leu Ala Gln145 150 155 160Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr Gly Leu Asn Asp Gly Thr 165 170 175Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp Gly Ile Arg Trp Trp Gln 180 185 190Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile Val Leu Leu Asp Asp Glu 195 200 205Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr Trp Lys Gln Asp Ser Lys 210 215 220Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser Phe Pro Tyr Asn Lys Trp225 230 235 240Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys 245 250 255Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu Lys Trp Tyr Tyr Leu Lys 260 265 270Asp Asn Gly Ala Met Ala Thr Gly Trp Val Leu Val Gly Ser Glu Trp 275 280 285Tyr Tyr Met Asp Asp Ser Gly Ala Met Val Thr Gly Trp Val Lys Tyr 290 295 300Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu Arg Gly Asn Met Val Ser305 310 315 320Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp Tyr Phe Met Asn Thr Asn 325 330 335Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr Lys Glu Pro Asp Gly Leu 340 345 350Ile Thr Val Ala 35575369PRTUnknownCecropin P1-Cpl1 75Ser Trp Leu Ser Lys Thr Ala Lys Lys Leu Glu Asn Ser Ala Lys Lys1 5 10 15Arg Ile Ser Glu Gly Ile Ala Ile Ala Ile Gln Gly Gly Pro Arg Val 20 25 30Lys Lys Asn Asp Leu Phe Val Asp Val Ser Ser His Asn Gly Tyr Asp 35 40 45Ile Thr Gly Ile Leu Glu Gln Met Gly Thr Thr Asn Thr Ile Ile Lys 50 55 60Ile Ser Glu Ser Thr Thr Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val65 70 75 80Glu Gln Ser Asn Pro Ile Gly Phe Tyr His Phe Ala Arg Phe Gly Gly 85 90 95Asp Val Ala Glu Ala Glu Arg Glu Ala Gln Phe Phe Leu Asp Asn Val 100 105 110Pro Met Gln Val Lys Tyr Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser 115 120 125Gly Asp Ala Gln Ala Asn Thr Asn Ala Cys Leu Arg Phe Met Gln Met 130 135 140Ile Ala Asp Ala Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe145 150 155 160Thr His Asp Asn Val Asp Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn 165 170 175Ser Leu Trp Ile Ala Gly Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe 180 185 190Glu Tyr Phe Pro Ser Met Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser 195 200 205Asn Pro Phe Asp Lys Asn Ile Val Leu Leu Asp Asp Glu Glu Asp Asp 210 215 220Lys Pro Lys Thr Ala Gly Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp225 230 235 240Phe Arg Arg Asn Asn Gly Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile 245 250 255Gly Gly Val Trp Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser 260 265 270Glu Trp Leu Lys Asp Asn Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly 275 280 285Ala Met Ala Thr Gly Trp Val Leu Val Gly Ser Glu Trp Tyr Tyr Met 290 295 300Asp Asp Ser Gly Ala Met Val Thr Gly Trp Val Lys Tyr Lys Asn Asn305 310 315 320Trp Tyr Tyr Met Thr Asn Glu Arg Gly Asn Met Val Ser Asn Glu Phe 325 330 335Ile Lys Ser Gly Lys Gly Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu 340 345 350Ala Asp Asn Pro Ser Phe Thr Lys Glu Pro Asp Gly Leu Ile Thr Val 355 360 365Ala 76361PRTUnknownMagainin-Cpl1 76Gly Ile Gly Lys Phe Leu His Ser Ala Lys Lys Phe Gly Lys Ala Phe1 5 10 15Val Gly Glu Ile Met Asn Ser Val Lys Lys Asn Asp Leu Phe Val Asp 20 25 30Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln Met 35 40 45Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr Leu 50 55 60Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile Gly Phe65 70 75 80Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu Arg Glu 85 90 95Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr Leu Val 100 105 110Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr Asn 115 120 125Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr Lys Pro 130 135 140Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp Tyr Gln145 150 155 160Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr Gly 165 170 175Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp Gly 180 185 190Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile Val 195 200 205Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr Trp 210 215 220Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser Phe225 230 235 240Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe Asp 245 250 255Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu Lys 260 265 270Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp Val Leu 275 280 285Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met Val Thr 290 295 300Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu Arg305 310 315 320Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp Tyr 325 330 335Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr Lys 340 345 350Glu Pro Asp Gly Leu Ile Thr Val Ala 355 36077363PRTUnknownPleurocidin-Cpl1 77Gly Trp Gly Ser Phe Phe Lys Lys Ala Ala His Val Gly Lys His Val1 5 10 15Gly Lys Ala Ala Leu Thr His Tyr Leu Val Lys Lys Asn Asp Leu Phe 20 25 30Val Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu 35 40 45Gln Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr 50 55 60Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile65 70 75 80Gly Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu 85 90 95Arg Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr 100 105 110Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn 115 120 125Thr Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr 130 135 140Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp145 150 155 160Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly 165 170 175Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met 180 185 190Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn 195 200 205Ile Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly 210 215 220Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly225 230 235 240Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr 245 250 255Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn 260 265 270Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp 275 280 285Val Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met 290 295 300Val Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn305 310 315 320Glu Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly 325 330 335Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe 340 345 350Thr Lys Glu Pro Asp Gly Leu Ile Thr Val Ala 355 36078374PRTUnknownCecropin A (A.aegypti)-Cpl1 78Gly Gly Leu Lys Lys Leu Gly Lys Lys Leu Glu Gly Ala Gly Lys Arg1 5 10 15Val Phe Asn Ala Ala Glu Lys Ala Leu Pro Val Val Ala Gly Ala Lys 20 25 30Ala Leu Arg Lys Val Lys Lys Asn Asp Leu Phe Val Asp Val Ser Ser 35 40 45His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln Met Gly Thr Thr 50 55 60Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr Leu Asn Pro Cys65 70 75 80Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile Gly Phe Tyr His Phe 85 90 95Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu Arg Glu Ala Gln Phe 100 105 110Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr Leu Val Leu Asp Tyr 115 120 125Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr Asn Ala Cys Leu 130 135 140Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr Lys Pro Ile Tyr Tyr145 150 155 160Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp Tyr Gln Gln Ile Leu 165 170 175Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr Gly Leu Asn Asp 180 185 190Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp Gly Ile Arg Trp 195 200 205Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile Val Leu Leu Asp 210 215 220Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr Trp Lys Gln Asp225 230 235 240Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser Phe Pro Tyr Asn 245 250 255Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe Asp Ser Lys Gly 260 265 270Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu Lys Trp Tyr Tyr 275 280 285Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp Val Leu Val Gly Ser 290 295 300Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met Val Thr Gly Trp Val305 310 315 320Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu Arg Gly Asn Met 325 330 335Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp Tyr Phe Met Asn 340 345 350Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr Lys Glu Pro Asp 355 360 365Gly Leu Ile Thr Val Ala 37079378PRTUnknownCecropin A (D.melanogaster)-Cpl1 79Gly Trp Leu Lys Lys Ile Gly Lys Lys Ile Glu Arg Val Gly Gln His1 5 10 15Thr Arg Asp Ala Thr Ile Gln Gly Leu Gly Ile Pro Gln Gln Ala Ala 20 25 30Asn Val Ala Ala Thr Ala Arg Gly Val Lys Lys Asn Asp Leu Phe Val 35 40 45Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln 50 55 60Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr65 70 75 80Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile Gly 85 90 95Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu Arg 100 105 110Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr Leu 115 120 125Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr 130 135 140Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr Lys145 150 155 160Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp Tyr 165 170 175Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr 180 185 190Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp 195 200 205Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile 210 215 220Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr225 230 235 240Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser 245 250 255Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe 260 265 270Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu 275 280 285Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp Val 290

295 300Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met Val305 310 315 320Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu 325 330 335Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp 340 345 350Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr 355 360 365Lys Glu Pro Asp Gly Leu Ile Thr Val Ala 370 37580359PRTUnknownBuforinII-Cpl1 80Thr Arg Ser Ser Arg Ala Gly Leu Gln Phe Pro Val Gly Arg Val His1 5 10 15Arg Leu Leu Arg Lys Val Lys Lys Asn Asp Leu Phe Val Asp Val Ser 20 25 30Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln Met Gly Thr 35 40 45Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr Leu Asn Pro 50 55 60Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile Gly Phe Tyr His65 70 75 80Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu Arg Glu Ala Gln 85 90 95Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr Leu Val Leu Asp 100 105 110Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr Asn Ala Cys 115 120 125Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr Lys Pro Ile Tyr 130 135 140Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp Tyr Gln Gln Ile145 150 155 160Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr Gly Leu Asn 165 170 175Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp Gly Ile Arg 180 185 190Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile Val Leu Leu 195 200 205Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr Trp Lys Gln 210 215 220Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser Phe Pro Tyr225 230 235 240Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe Asp Ser Lys 245 250 255Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu Lys Trp Tyr 260 265 270Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp Val Leu Val Gly 275 280 285Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met Val Thr Gly Trp 290 295 300Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu Arg Gly Asn305 310 315 320Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp Tyr Phe Met 325 330 335Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr Lys Glu Pro 340 345 350Asp Gly Leu Ile Thr Val Ala 35581377PRTUnknownSarcotoxin IA-Cpl1 81Gly Trp Leu Lys Lys Ile Gly Lys Lys Ile Glu Arg Val Gly Gln His1 5 10 15Thr Arg Asp Ala Thr Ile Gln Gly Leu Gly Ile Ala Gln Gln Ala Ala 20 25 30Asn Val Ala Ala Thr Ala Arg Val Lys Lys Asn Asp Leu Phe Val Asp 35 40 45Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln Met 50 55 60Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr Leu65 70 75 80Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile Gly Phe 85 90 95Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu Arg Glu 100 105 110Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr Leu Val 115 120 125Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr Asn 130 135 140Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr Lys Pro145 150 155 160Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp Tyr Gln 165 170 175Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr Gly 180 185 190Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp Gly 195 200 205Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile Val 210 215 220Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr Trp225 230 235 240Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser Phe 245 250 255Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe Asp 260 265 270Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu Lys 275 280 285Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp Val Leu 290 295 300Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met Val Thr305 310 315 320Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu Arg 325 330 335Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp Tyr 340 345 350Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr Lys 355 360 365Glu Pro Asp Gly Leu Ile Thr Val Ala 370 37582347PRTUnknownPK-Cpl1 82Lys Arg Lys Lys Arg Lys Lys Arg Lys Val Lys Lys Asn Asp Leu Phe1 5 10 15Val Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu 20 25 30Gln Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr 35 40 45Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile 50 55 60Gly Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu65 70 75 80Arg Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr 85 90 95Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn 100 105 110Thr Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr 115 120 125Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp 130 135 140Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly145 150 155 160Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met 165 170 175Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn 180 185 190Ile Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly 195 200 205Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly 210 215 220Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr225 230 235 240Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn 245 250 255Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp 260 265 270Val Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met 275 280 285Val Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn 290 295 300Glu Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly305 310 315 320Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe 325 330 335Thr Lys Glu Pro Asp Gly Leu Ile Thr Val Ala 340 34583345PRTUnknownSynthetic peptide-Ply511 83Phe Phe Val Ala Pro Val Lys Tyr Thr Val Glu Asn Lys Ile Ile Ala1 5 10 15Gly Leu Pro Lys Gly Lys Leu Lys Gly Ala Asn Phe Val Ile Ala His 20 25 30Glu Thr Ala Asn Ser Lys Ser Thr Ile Asp Asn Glu Val Ser Tyr Met 35 40 45Thr Arg Asn Trp Lys Asn Ala Phe Val Thr His Phe Val Gly Gly Gly 50 55 60Gly Arg Val Val Gln Val Ala Asn Val Asn Tyr Val Ser Trp Gly Ala65 70 75 80Gly Gln Tyr Ala Asn Ser Tyr Ser Tyr Ala Gln Val Glu Leu Cys Arg 85 90 95Thr Ser Asn Ala Thr Thr Phe Lys Lys Asp Tyr Glu Val Tyr Cys Gln 100 105 110Leu Leu Val Asp Leu Ala Lys Lys Ala Gly Ile Pro Ile Thr Leu Asp 115 120 125Ser Gly Ser Lys Thr Ser Asp Lys Gly Ile Lys Ser His Lys Trp Val 130 135 140Ala Asp Lys Leu Gly Gly Thr Thr His Gln Asp Pro Tyr Ala Tyr Leu145 150 155 160Ser Ser Trp Gly Ile Ser Lys Ala Gln Phe Ala Ser Asp Leu Ala Lys 165 170 175Val Ser Gly Gly Gly Asn Thr Gly Thr Ala Pro Ala Lys Pro Ser Thr 180 185 190Pro Ala Pro Lys Pro Ser Thr Pro Ser Thr Asn Leu Asp Lys Leu Gly 195 200 205Leu Val Asp Tyr Met Asn Ala Lys Lys Met Asp Ser Ser Tyr Ser Asn 210 215 220Arg Asp Lys Leu Ala Lys Gln Tyr Gly Ile Ala Asn Tyr Ser Gly Thr225 230 235 240Ala Ser Gln Asn Thr Thr Leu Leu Ser Lys Ile Lys Gly Gly Ala Pro 245 250 255Lys Pro Ser Thr Pro Ala Pro Lys Pro Ser Thr Ser Thr Ala Lys Lys 260 265 270Ile Tyr Phe Pro Pro Asn Lys Gly Asn Trp Ser Val Tyr Pro Thr Asn 275 280 285Lys Ala Pro Val Lys Ala Asn Ala Ile Gly Ala Ile Asn Pro Thr Lys 290 295 300Phe Gly Gly Leu Thr Tyr Thr Ile Gln Lys Asp Arg Gly Asn Gly Val305 310 315 320Tyr Glu Ile Gln Thr Asp Gln Phe Gly Arg Val Gln Val Tyr Gly Ala 325 330 335Pro Ser Thr Gly Ala Val Ile Lys Lys 340 34584503PRTUnknownPK-LysK (PK N-terminal) 84Lys Arg Lys Lys Arg Lys Lys Arg Lys Ala Lys Thr Gln Ala Glu Ile1 5 10 15Asn Lys Arg Leu Asp Ala Tyr Ala Lys Gly Thr Val Asp Ser Pro Tyr 20 25 30Arg Val Lys Lys Ala Thr Ser Tyr Asp Pro Ser Phe Gly Val Met Glu 35 40 45Ala Gly Ala Ile Asp Ala Asp Gly Tyr Tyr His Ala Gln Cys Gln Asp 50 55 60Leu Ile Thr Asp Tyr Val Leu Trp Leu Thr Asp Asn Lys Val Arg Thr65 70 75 80Trp Gly Asn Ala Lys Asp Gln Ile Lys Gln Ser Tyr Gly Thr Gly Phe 85 90 95Lys Ile His Glu Asn Lys Pro Ser Thr Val Pro Lys Lys Gly Trp Ile 100 105 110Ala Val Phe Thr Ser Gly Ser Tyr Glu Gln Trp Gly His Ile Gly Ile 115 120 125Val Tyr Asp Gly Gly Asn Thr Ser Thr Phe Thr Ile Leu Glu Gln Asn 130 135 140Trp Asn Gly Tyr Ala Asn Lys Lys Pro Thr Lys Arg Val Asp Asn Tyr145 150 155 160Tyr Gly Leu Thr His Phe Ile Glu Ile Pro Val Lys Ala Gly Thr Thr 165 170 175Val Lys Lys Glu Thr Ala Lys Lys Ser Ala Ser Lys Thr Pro Ala Pro 180 185 190Lys Lys Lys Ala Thr Leu Lys Val Ser Lys Asn His Ile Asn Tyr Thr 195 200 205Met Asp Lys Arg Gly Lys Lys Pro Glu Gly Met Val Ile His Asn Asp 210 215 220Ala Gly Arg Ser Ser Gly Gln Gln Tyr Glu Asn Ser Leu Ala Asn Ala225 230 235 240Gly Tyr Ala Arg Tyr Ala Asn Gly Ile Ala His Tyr Tyr Gly Ser Glu 245 250 255Gly Tyr Val Trp Glu Ala Ile Asp Ala Lys Asn Gln Ile Ala Trp His 260 265 270Thr Gly Asp Gly Thr Gly Ala Asn Ser Gly Asn Phe Arg Phe Ala Gly 275 280 285Ile Glu Val Cys Gln Ser Met Ser Ala Ser Asp Ala Gln Phe Leu Lys 290 295 300Asn Glu Gln Ala Val Phe Gln Phe Thr Ala Glu Lys Phe Lys Glu Trp305 310 315 320Gly Leu Thr Pro Asn Arg Lys Thr Val Arg Leu His Met Glu Phe Val 325 330 335Pro Thr Ala Cys Pro His Arg Ser Met Val Leu His Thr Gly Phe Asn 340 345 350Pro Val Thr Gln Gly Arg Pro Ser Gln Ala Ile Met Asn Lys Leu Lys 355 360 365Asp Tyr Phe Ile Lys Gln Ile Lys Asn Tyr Met Asp Lys Gly Thr Ser 370 375 380Ser Ser Thr Val Val Lys Asp Gly Lys Thr Ser Ser Ala Ser Thr Pro385 390 395 400Ala Thr Arg Pro Val Thr Gly Ser Trp Lys Lys Asn Gln Tyr Gly Thr 405 410 415Trp Tyr Lys Pro Glu Asn Ala Thr Phe Val Asn Gly Asn Gln Pro Ile 420 425 430Val Thr Arg Ile Gly Ser Pro Phe Leu Asn Ala Pro Val Gly Gly Asn 435 440 445Leu Pro Ala Gly Ala Thr Ile Val Tyr Asp Glu Val Cys Ile Gln Ala 450 455 460Gly His Ile Trp Ile Gly Tyr Asn Ala Tyr Asn Gly Asn Arg Val Tyr465 470 475 480Cys Pro Val Arg Thr Cys Gln Gly Val Pro Pro Asn Gln Ile Pro Gly 485 490 495Val Ala Trp Gly Val Phe Lys 50085512PRTUnknownPK2-LysK 85Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys1 5 10 15Arg Lys Ala Lys Thr Gln Ala Glu Ile Asn Lys Arg Leu Asp Ala Tyr 20 25 30Ala Lys Gly Thr Val Asp Ser Pro Tyr Arg Val Lys Lys Ala Thr Ser 35 40 45Tyr Asp Pro Ser Phe Gly Val Met Glu Ala Gly Ala Ile Asp Ala Asp 50 55 60Gly Tyr Tyr His Ala Gln Cys Gln Asp Leu Ile Thr Asp Tyr Val Leu65 70 75 80Trp Leu Thr Asp Asn Lys Val Arg Thr Trp Gly Asn Ala Lys Asp Gln 85 90 95Ile Lys Gln Ser Tyr Gly Thr Gly Phe Lys Ile His Glu Asn Lys Pro 100 105 110Ser Thr Val Pro Lys Lys Gly Trp Ile Ala Val Phe Thr Ser Gly Ser 115 120 125Tyr Glu Gln Trp Gly His Ile Gly Ile Val Tyr Asp Gly Gly Asn Thr 130 135 140Ser Thr Phe Thr Ile Leu Glu Gln Asn Trp Asn Gly Tyr Ala Asn Lys145 150 155 160Lys Pro Thr Lys Arg Val Asp Asn Tyr Tyr Gly Leu Thr His Phe Ile 165 170 175Glu Ile Pro Val Lys Ala Gly Thr Thr Val Lys Lys Glu Thr Ala Lys 180 185 190Lys Ser Ala Ser Lys Thr Pro Ala Pro Lys Lys Lys Ala Thr Leu Lys 195 200 205Val Ser Lys Asn His Ile Asn Tyr Thr Met Asp Lys Arg Gly Lys Lys 210 215 220Pro Glu Gly Met Val Ile His Asn Asp Ala Gly Arg Ser Ser Gly Gln225 230 235 240Gln Tyr Glu Asn Ser Leu Ala Asn Ala Gly Tyr Ala Arg Tyr Ala Asn 245 250 255Gly Ile Ala His Tyr Tyr Gly Ser Glu Gly Tyr Val Trp Glu Ala Ile 260 265 270Asp Ala Lys Asn Gln Ile Ala Trp His Thr Gly Asp Gly Thr Gly Ala 275 280 285Asn Ser Gly Asn Phe Arg Phe Ala Gly Ile Glu Val Cys Gln Ser Met 290 295 300Ser Ala Ser Asp Ala Gln Phe Leu Lys Asn Glu Gln Ala Val Phe Gln305 310 315 320Phe Thr Ala Glu Lys Phe Lys Glu Trp Gly Leu Thr Pro Asn Arg Lys 325 330 335Thr Val Arg Leu His Met Glu Phe Val Pro Thr Ala Cys Pro His Arg 340 345 350Ser Met Val Leu His Thr Gly Phe Asn Pro Val Thr Gln Gly Arg Pro 355 360 365Ser Gln Ala Ile Met Asn Lys Leu Lys Asp Tyr Phe Ile Lys Gln Ile 370 375 380Lys Asn Tyr Met Asp Lys Gly Thr Ser Ser Ser Thr Val Val Lys Asp385 390 395 400Gly Lys Thr Ser Ser Ala Ser Thr Pro Ala Thr Arg Pro Val Thr Gly 405 410 415Ser Trp Lys Lys Asn Gln Tyr Gly Thr Trp Tyr Lys Pro Glu Asn Ala 420 425 430Thr Phe Val Asn Gly Asn Gln Pro Ile Val

Thr Arg Ile Gly Ser Pro 435 440 445Phe Leu Asn Ala Pro Val Gly Gly Asn Leu Pro Ala Gly Ala Thr Ile 450 455 460Val Tyr Asp Glu Val Cys Ile Gln Ala Gly His Ile Trp Ile Gly Tyr465 470 475 480Asn Ala Tyr Asn Gly Asn Arg Val Tyr Cys Pro Val Arg Thr Cys Gln 485 490 495Gly Val Pro Pro Asn Gln Ile Pro Gly Val Ala Trp Gly Val Phe Lys 500 505 51086259PRTUnknownPK-Lss 86Lys Arg Lys Lys Arg Lys Lys Arg Lys Ala His Glu His Ser Ala Gln1 5 10 15Trp Leu Asn Asn Tyr Lys Lys Gly Tyr Gly Tyr Gly Pro Tyr Pro Leu 20 25 30Gly Ile Asn Gly Gly Met His Tyr Gly Val Asp Phe Phe Met Asn Ile 35 40 45Gly Thr Pro Val Lys Ala Ile Ser Ser Gly Lys Ile Val Glu Ala Gly 50 55 60Trp Ser Asn Tyr Gly Gly Gly Asn Gln Ile Gly Leu Ile Glu Asn Asp65 70 75 80Gly Val His Arg Gln Trp Tyr Met His Leu Ser Lys Tyr Asn Val Lys 85 90 95Val Gly Asp Tyr Val Lys Ala Gly Gln Ile Ile Gly Trp Ser Gly Ser 100 105 110Thr Gly Tyr Ser Thr Ala Pro His Leu His Phe Gln Arg Met Val Asn 115 120 125Ser Phe Ser Asn Ser Thr Ala Gln Asp Pro Met Pro Phe Leu Lys Ser 130 135 140Ala Gly Tyr Gly Lys Ala Gly Gly Thr Val Thr Pro Thr Pro Asn Thr145 150 155 160Gly Trp Lys Thr Asn Lys Tyr Gly Thr Leu Tyr Lys Ser Glu Ser Ala 165 170 175Ser Phe Thr Pro Asn Thr Asp Ile Ile Thr Arg Thr Thr Gly Pro Phe 180 185 190Arg Ser Met Pro Gln Ser Gly Val Leu Lys Ala Gly Gln Thr Ile His 195 200 205Tyr Asp Glu Val Met Lys Gln Asp Gly His Val Trp Val Gly Tyr Thr 210 215 220Gly Asn Ser Gly Gln Arg Ile Tyr Leu Pro Val Arg Thr Trp Asn Lys225 230 235 240Ser Thr Asn Thr Leu Gly Val Leu Trp Gly Thr Ile Lys Leu Val Pro 245 250 255Arg Gly Ser87268PRTUnknownPK2-Lss 87Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys1 5 10 15Arg Lys Ala His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys Lys 20 25 30Gly Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met His 35 40 45Tyr Gly Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala Ile 50 55 60Ser Ser Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly Gly65 70 75 80Asn Gln Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp Tyr 85 90 95Met His Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys Ala 100 105 110Gly Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala Pro 115 120 125His Leu His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr Ala 130 135 140Gln Asp Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Lys Ala Gly145 150 155 160Gly Thr Val Thr Pro Thr Pro Asn Thr Gly Trp Lys Thr Asn Lys Tyr 165 170 175Gly Thr Leu Tyr Lys Ser Glu Ser Ala Ser Phe Thr Pro Asn Thr Asp 180 185 190Ile Ile Thr Arg Thr Thr Gly Pro Phe Arg Ser Met Pro Gln Ser Gly 195 200 205Val Leu Lys Ala Gly Gln Thr Ile His Tyr Asp Glu Val Met Lys Gln 210 215 220Asp Gly His Val Trp Val Gly Tyr Thr Gly Asn Ser Gly Gln Arg Ile225 230 235 240Tyr Leu Pro Val Arg Thr Trp Asn Lys Ser Thr Asn Thr Leu Gly Val 245 250 255Leu Trp Gly Thr Ile Lys Leu Val Pro Arg Gly Ser 260 26588303PRTUnknownWalmagh1-PA6gp20 88Gly Phe Phe Ile Pro Ala Val Ile Leu Pro Ser Ile Ala Phe Leu Ile1 5 10 15Val Pro Val Arg Tyr Ile Pro Ala Ala His His Ser Ala Gly Ser Asn 20 25 30Asn Pro Val Asn Arg Val Val Ile His Ala Thr Cys Pro Asp Val Gly 35 40 45Phe Pro Ser Ala Ser Arg Lys Gly Arg Ala Val Ser Thr Ala Asn Tyr 50 55 60Phe Ala Ser Pro Ser Ser Gly Gly Ser Ala His Tyr Val Cys Asp Ile65 70 75 80Gly Glu Thr Val Gln Cys Leu Ser Glu Ser Thr Ile Gly Trp His Ala 85 90 95Pro Pro Asn Pro His Ser Leu Gly Ile Glu Ile Cys Ala Asp Gly Gly 100 105 110Ser His Ala Ser Phe Arg Val Pro Gly His Ala Tyr Thr Arg Glu Gln 115 120 125Trp Leu Asp Pro Gln Val Trp Pro Ala Val Glu Arg Ala Ala Val Leu 130 135 140Cys Arg Arg Leu Cys Asp Lys Tyr Asn Val Pro Lys Arg Lys Leu Ser145 150 155 160Ala Ala Asp Leu Lys Ala Gly Arg Arg Gly Val Cys Gly His Val Asp 165 170 175Val Thr Asp Ala Trp His Gln Ser Asp His Asp Asp Pro Gly Pro Trp 180 185 190Phe Pro Trp Asp Lys Phe Met Ala Val Val Asn Gly Gly Ser Gly Asp 195 200 205Ser Gly Glu Leu Thr Val Ala Asp Val Lys Ala Leu His Asp Gln Ile 210 215 220Lys Gln Leu Ser Ala Gln Leu Thr Gly Ser Val Asn Lys Leu His His225 230 235 240Asp Val Gly Val Val Gln Val Gln Asn Gly Asp Leu Gly Lys Arg Val 245 250 255Asp Ala Leu Ser Trp Val Lys Asn Pro Val Thr Gly Lys Leu Trp Arg 260 265 270Thr Lys Asp Ala Leu Trp Ser Val Trp Tyr Tyr Val Leu Glu Cys Arg 275 280 285Ser Arg Leu Asp Arg Leu Glu Ser Ala Val Asn Asp Leu Lys Lys 290 295 30089503PRTUnknownLysK-PK (PK C-terminal) 89Ala Lys Thr Gln Ala Glu Ile Asn Lys Arg Leu Asp Ala Tyr Ala Lys1 5 10 15Gly Thr Val Asp Ser Pro Tyr Arg Val Lys Lys Ala Thr Ser Tyr Asp 20 25 30Pro Ser Phe Gly Val Met Glu Ala Gly Ala Ile Asp Ala Asp Gly Tyr 35 40 45Tyr His Ala Gln Cys Gln Asp Leu Ile Thr Asp Tyr Val Leu Trp Leu 50 55 60Thr Asp Asn Lys Val Arg Thr Trp Gly Asn Ala Lys Asp Gln Ile Lys65 70 75 80Gln Ser Tyr Gly Thr Gly Phe Lys Ile His Glu Asn Lys Pro Ser Thr 85 90 95Val Pro Lys Lys Gly Trp Ile Ala Val Phe Thr Ser Gly Ser Tyr Glu 100 105 110Gln Trp Gly His Ile Gly Ile Val Tyr Asp Gly Gly Asn Thr Ser Thr 115 120 125Phe Thr Ile Leu Glu Gln Asn Trp Asn Gly Tyr Ala Asn Lys Lys Pro 130 135 140Thr Lys Arg Val Asp Asn Tyr Tyr Gly Leu Thr His Phe Ile Glu Ile145 150 155 160Pro Val Lys Ala Gly Thr Thr Val Lys Lys Glu Thr Ala Lys Lys Ser 165 170 175Ala Ser Lys Thr Pro Ala Pro Lys Lys Lys Ala Thr Leu Lys Val Ser 180 185 190Lys Asn His Ile Asn Tyr Thr Met Asp Lys Arg Gly Lys Lys Pro Glu 195 200 205Gly Met Val Ile His Asn Asp Ala Gly Arg Ser Ser Gly Gln Gln Tyr 210 215 220Glu Asn Ser Leu Ala Asn Ala Gly Tyr Ala Arg Tyr Ala Asn Gly Ile225 230 235 240Ala His Tyr Tyr Gly Ser Glu Gly Tyr Val Trp Glu Ala Ile Asp Ala 245 250 255Lys Asn Gln Ile Ala Trp His Thr Gly Asp Gly Thr Gly Ala Asn Ser 260 265 270Gly Asn Phe Arg Phe Ala Gly Ile Glu Val Cys Gln Ser Met Ser Ala 275 280 285Ser Asp Ala Gln Phe Leu Lys Asn Glu Gln Ala Val Phe Gln Phe Thr 290 295 300Ala Glu Lys Phe Lys Glu Trp Gly Leu Thr Pro Asn Arg Lys Thr Val305 310 315 320Arg Leu His Met Glu Phe Val Pro Thr Ala Cys Pro His Arg Ser Met 325 330 335Val Leu His Thr Gly Phe Asn Pro Val Thr Gln Gly Arg Pro Ser Gln 340 345 350Ala Ile Met Asn Lys Leu Lys Asp Tyr Phe Ile Lys Gln Ile Lys Asn 355 360 365Tyr Met Asp Lys Gly Thr Ser Ser Ser Thr Val Val Lys Asp Gly Lys 370 375 380Thr Ser Ser Ala Ser Thr Pro Ala Thr Arg Pro Val Thr Gly Ser Trp385 390 395 400Lys Lys Asn Gln Tyr Gly Thr Trp Tyr Lys Pro Glu Asn Ala Thr Phe 405 410 415Val Asn Gly Asn Gln Pro Ile Val Thr Arg Ile Gly Ser Pro Phe Leu 420 425 430Asn Ala Pro Val Gly Gly Asn Leu Pro Ala Gly Ala Thr Ile Val Tyr 435 440 445Asp Glu Val Cys Ile Gln Ala Gly His Ile Trp Ile Gly Tyr Asn Ala 450 455 460Tyr Asn Gly Asn Arg Val Tyr Cys Pro Val Arg Thr Cys Gln Gly Val465 470 475 480Pro Pro Asn Gln Ile Pro Gly Val Ala Trp Gly Val Phe Lys Lys Arg 485 490 495Lys Lys Arg Lys Lys Arg Lys 50090252PRTUnknownLss-PK (PK C-terminal) 90His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys Lys Gly Tyr Gly1 5 10 15Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met His Tyr Gly Val 20 25 30Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala Ile Ser Ser Gly 35 40 45Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly Gly Asn Gln Ile 50 55 60Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp Tyr Met His Leu65 70 75 80Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys Ala Gly Gln Ile 85 90 95Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala Pro His Leu His 100 105 110Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr Ala Gln Asp Pro 115 120 125Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Lys Ala Gly Gly Thr Val 130 135 140Thr Pro Thr Pro Asn Thr Gly Trp Lys Thr Asn Lys Tyr Gly Thr Leu145 150 155 160Tyr Lys Ser Glu Ser Ala Ser Phe Thr Pro Asn Thr Asp Ile Ile Thr 165 170 175Arg Thr Thr Gly Pro Phe Arg Ser Met Pro Gln Ser Gly Val Leu Lys 180 185 190Ala Gly Gln Thr Ile His Tyr Asp Glu Val Met Lys Gln Asp Gly His 195 200 205Val Trp Val Gly Tyr Thr Gly Asn Ser Gly Gln Arg Ile Tyr Leu Pro 210 215 220Val Arg Thr Trp Asn Lys Ser Thr Asn Thr Leu Gly Val Leu Trp Gly225 230 235 240Thr Ile Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys 245 250911017DNAUnknownCpl-1 91atggtgaaaa aaaacgatct gttcgttgac gtgtcttccc acaacggtta cgatatcact 60ggcattctgg aacagatggg caccaccaac accattatca aaatctccga aagcacgacc 120tatctgaacc cgtgtctgtc tgcccaggta gaacagtcta acccaattgg cttctaccat 180ttcgcacgtt tcggtggtga tgtagccgaa gcggaacgtg aagcgcagtt ctttctggat 240aacgtgccga tgcaggttaa atacctggtt ctggactatg aagacgatcc gtctggtgac 300gcacaggcaa acaccaacgc gtgcctgcgt ttcatgcaga tgattgcaga cgctggctac 360aaaccgatct attactctta caaaccgttc acccacgata acgtcgatta ccagcagatt 420ctggcgcagt ttccgaactc tctgtggatc gcaggttatg gcctgaacga cggtactgcg 480aactttgagt atttcccaag catggacggc atccgctggt ggcagtattc ctccaacccg 540ttcgacaaaa acatcgtact gctggacgac gaagaggacg acaaaccgaa aactgctggt 600acctggaaac aggatagcaa aggctggtgg tttcgtcgta acaacggttc ttttccgtac 660aacaaatggg aaaaaatcgg tggtgtttgg tattacttcg actccaaagg ctactgcctg 720acgagcgaat ggctgaaaga taacgagaaa tggtactatc tcaaagacaa cggtgccatg 780gctactggtt gggttctggt tggttctgag tggtactaca tggacgattc tggtgctatg 840gttaccggct gggtgaaata caaaaacaac tggtattaca tgacgaacga acgcggtaac 900atggtgagca acgaattcat caaatccggc aaaggctggt acttcatgaa cactaacggt 960gaactggcgg ataacccgtc tttcaccaaa gaaccggatg gcctgatcac cgtcgct 1017921023DNAUnknownPly511 92atggtgaaat acaccgtgga aaacaaaatc atcgcaggcc tgccgaaagg caaactgaaa 60ggcgcgaact tcgttattgc tcatgaaacc gcaaactcca aatccaccat cgacaacgaa 120gtcagctata tgactcgcaa ctggaaaaac gcgtttgtga ctcactttgt aggtggcggt 180ggccgtgtcg tacaggtagc gaacgttaac tacgtaagct ggggtgcagg tcagtatgct 240aacagctatt cctacgcgca ggtagaactg tgtcgtacgt ctaacgcgac cacgttcaaa 300aaagactacg aggtttattg ccagctgctg gttgacctgg ccaaaaaagc tggtatccca 360atcaccctgg attctggctc caaaacctct gacaaaggca tcaaatccca caaatgggtt 420gctgacaaac tgggcggtac cactcaccag gacccgtatg cttacctgtc ttcttggggc 480atttctaaag cccagttcgc ctctgatctg gctaaagttt ctggcggtgg taacaccggt 540actgctccag caaaaccgtc tactccggca ccaaaaccgt ctactccgtc tactaacctg 600gacaaactgg gcctggtgga ttacatgaac gcgaaaaaaa tggatagcag ctactccaac 660cgtgacaaac tggcgaaaca gtacggtatc gcaaactata gcggtaccgc ctctcagaac 720accaccctgc tctctaaaat caaaggcggt gcaccaaaac caagcactcc agcgccaaaa 780ccgtctacct ccacggctaa aaaaatctac ttcccgccga acaaaggtaa ctggtccgta 840tacccgacca acaaagctcc ggtgaaagcc aacgcaattg gtgctatcaa cccgaccaaa 900ttcggtggcc tgacctatac gattcagaaa gatcgcggca acggtgtgta cgaaattcag 960accgatcagt tcggtcgtgt tcaggtttac ggtgctccgt ctaccggtgc ggttatcaaa 1020aaa 1023931485DNAUnknownLysK 93atggccaaaa cccaggctga aatcaacaaa cgtctggacg cgtacgctaa aggcactgtt 60gattctccgt accgtgtgaa aaaagccacc tcctatgatc cgtcttttgg tgtaatggaa 120gcgggcgcta ttgacgctga cggctattac catgcccagt gccaggatct gatcacggac 180tatgttctgt ggctgaccga caacaaagtt cgtacctggg gtaacgcgaa agatcagatc 240aaacagtcct acggcaccgg tttcaaaatc cacgagaaca aaccgtccac cgttccgaaa 300aaaggttgga tcgctgtctt cacctctggc tcctatgaac agtggggtca catcggtatc 360gtgtacgatg gtggtaacac cagcacgttc accatcctgg aacagaactg gaacggttac 420gcgaacaaaa aaccgaccaa acgtgtggat aactactacg gcctgacgca cttcattgaa 480atcccggtga aagctggtac taccgtgaaa aaagagacgg cgaaaaaatc tgcctctaaa 540actccggcac cgaaaaaaaa agccaccctg aaagtctcta aaaaccacat caactacacg 600atggacaaac gcggtaaaaa accggaaggc atggtcattc acaacgatgc tggtcgctct 660tccggccagc agtatgaaaa cagcctggct aacgcaggtt acgcacgtta cgcaaacggt 720attgcgcact actacggttc tgaaggctat gtgtgggaag ctatcgacgc gaaaaaccag 780attgcgtggc acaccggcga cggtaccggc gctaactctg gcaacttccg ctttgcaggc 840attgaggtat gtcagtctat gtccgcgtct gatgcgcagt tcctgaaaaa cgaacaggct 900gtcttccagt tcactgcgga gaaattcaaa gaatggggtc tgactccgaa ccgcaaaact 960gtacgcctgc acatggaatt tgttccgact gcatgtccgc atcgtagcat ggttctgcac 1020actggcttta acccggttac tcagggtcgt ccgagccagg cgatcatgaa caaactgaaa 1080gactacttta tcaaacagat caaaaactac atggataaag gcaccagctc cagcaccgta 1140gttaaagatg gcaaaacttc tagcgcgtcc actccggcaa cccgtccggt tactggttct 1200tggaaaaaaa accagtatgg tacctggtac aaaccggaaa acgccacctt cgtaaacggc 1260aaccagccga ttgtaactcg tatcggttct ccgtttctga acgcgccggt tggcggcaac 1320ctgccggcag gtgctacgat tgtgtacgac gaagtttgca ttcaggcagg ccacatttgg 1380atcggctaca acgcgtataa cggtaaccgc gtttactgcc cggtacgtac ctgtcagggt 1440gttccgccga accagattcc gggcgtggca tggggtgttt tcaaa 148594735DNAUnknownLss 94atggcccatg agcattcagc ccaatggctc aataattata aaaaaggata tgggtatggt 60ccttatccct tggggattaa tggtggtatg cattatgggg tcgacttttt tatgaacatt 120ggtacccccg ttaaagcaat ctcatctggg aaaatagttg aagctggatg gtcaaactac 180ggtggcggca atcagattgg cctgatagaa aatgacggag ttcaccgtca gtggtacatg 240cacctttcga agtataacgt caaggtaggc gactatgtaa aggctggtca aattatcggt 300tggtcaggaa gtacaggata tagtaccgcg ccccacctcc atttccagcg gatggtgaac 360tcattctcga actctaccgc acaggatccg atgccgttcc tgaaaagtgc aggctatggc 420aaagctgggg gcacagtaac tcccaccccg aacaccggat ggaagacaaa taagtacggt 480acactttaca aaagcgagtc agcatcattt acaccgaata cggacatcat cacacgtact 540acaggaccgt tcaggtcgat gcctcaatct ggggtcctca aggctggaca gacgatacac 600tacgacgagg tcatgaagca ggacgggcat gtctgggtcg ggtacactgg aaactctgga 660caacgaattt atcttccggt tcgaacatgg aacaaatcaa cgaatacatt gggcgtgcta 720tgggggacca taaag 73595528DNAUnknownPseudin 1 95aacccgatta tcgatggcat tatcgcgctg gaaggaggtt acgtctttaa tccgaaagat 60aagggtggag caacacattg gggtattaca gaagcgacgg cacgagcaca tggttatgca 120ggagacatgc gtgatctaac tcatgccgaa gcctacgcaa tacttgagga ggattactgg 180atcaaaccgg gttttgatgt tatctcaacg ctgtcgtggc ctgtgagctt tgaattgtgt 240gatgcagcgg ttaacatagg tgcataccac cctagtgcct ggttacagag atggcttaac 300gtgttcaatc acgaaggcaa acgctatcca gacattcatg tagacggcaa cattggtccc

360aggactttag cagccttaga acattacttg gcttggagag ggcaagaagg tgaagctgta 420ctggtgaaag ctctgaattg cagccaaggg acctactatc taaacgtcgc tgagaagaac 480cacaacaacg aacagttcat ctacggttgg atcaagaatc gtgtgacc 5289681DNAUnknownWLBU2-Variant 96aaacgctggg ttaaacgcgt gaaacgtgtc aaacgttggg tcaaacgtgt tgtccgtgta 60gtgaaacgtt gggtgaaacg c 8197111DNAUnknownLL-37 97ctcctgggtg acttctttcg caaatccaaa gagaaaatcg gcaaagagtt caaacgtatc 60gtgcagcgca ttaaagactt tctgcgtaac ctggttccgc gtaccgaatc t 1119839DNAUnknownIndolicidin 98atcctgccgt ggaaatggcc gtggtggcca tggcgtcgc 399969DNAUnknownMagainin 99ggtatcggca aattcctgca ctccgcaaaa aaattcggca aagctttcgt gggcgaaatt 60atgaactct 6910075DNAUnknownPleurocidin 100ggctggggtt ctttctttaa aaaagcggct cacgttggca aacatgtagg taaagcagct 60ctgacccact atctg 75101108DNAUnknownCecropin A (A. aegypti) 101ggcggcctga aaaaactggg caaaaaactg gaaggtgccg gcaaacgtgt gttcaacgct 60gcagaaaaag cactgccggt tgtagctggt gctaaagctc tccgtaaa 108102120DNAUnknownCecropin A (D. melanogaster) 102ggctggctga aaaaaattgg caaaaaaatc gaacgcgtgg gccagcacac gcgtgatgca 60accatccagg gtctgggtat cccacagcag gcagctaacg tagccgcgac tgctcgtggt 120103117DNAUnknownSarcotoxin IA 103ggatggctca aaaagattgg caagaaaatc gagcgagtcg gtcagcatac gcgtgatgca 60actatccagg gtttaggtat cgcacagcaa gcagctaatg tagcagctac tgctcgg 11710427DNAUnknownPK 104aagcgtaaga aacgcaaaaa acgcaaa 2710515DNAUnknownSynthetic peptide 105ttctttgtgg cgccg 1510654DNAUnknownPK2 106aagcgtaaga aacgcaaaaa acgcaaaaaa cgcaaaaaac gcaagaaaag aaaa 54107373PRTUnknownPseudin1-Cpl1 107Met Gly Leu Asn Thr Leu Lys Lys Val Phe Gln Gly Leu His Glu Ala1 5 10 15Ile Lys Leu Ile Asn Asn His Val Gln Gly Ser Val Lys Lys Asn Asp 20 25 30Leu Phe Val Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile 35 40 45Leu Glu Gln Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser 50 55 60Thr Thr Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn65 70 75 80Pro Ile Gly Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu 85 90 95Ala Glu Arg Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val 100 105 110Lys Tyr Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln 115 120 125Ala Asn Thr Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala 130 135 140Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn145 150 155 160Val Asp Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile 165 170 175Ala Gly Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro 180 185 190Ser Met Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp 195 200 205Lys Asn Ile Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr 210 215 220Ala Gly Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn225 230 235 240Asn Gly Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp 245 250 255Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys 260 265 270Asp Asn Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr 275 280 285Gly Trp Val Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly 290 295 300Ala Met Val Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met305 310 315 320Thr Asn Glu Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly 325 330 335Lys Gly Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro 340 345 350Ser Phe Thr Lys Glu Pro Asp Gly Leu Ile Thr Val Ala Leu Glu His 355 360 365His His His His His 370108376PRTUnknownWLBU2-Variant-Cpl1 108Met Lys Arg Trp Val Lys Arg Val Lys Arg Val Lys Arg Trp Val Lys1 5 10 15Arg Val Val Arg Val Val Lys Arg Trp Val Lys Arg Gly Ser Val Lys 20 25 30Lys Asn Asp Leu Phe Val Asp Val Ser Ser His Asn Gly Tyr Asp Ile 35 40 45Thr Gly Ile Leu Glu Gln Met Gly Thr Thr Asn Thr Ile Ile Lys Ile 50 55 60Ser Glu Ser Thr Thr Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val Glu65 70 75 80Gln Ser Asn Pro Ile Gly Phe Tyr His Phe Ala Arg Phe Gly Gly Asp 85 90 95Val Ala Glu Ala Glu Arg Glu Ala Gln Phe Phe Leu Asp Asn Val Pro 100 105 110Met Gln Val Lys Tyr Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly 115 120 125Asp Ala Gln Ala Asn Thr Asn Ala Cys Leu Arg Phe Met Gln Met Ile 130 135 140Ala Asp Ala Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr145 150 155 160His Asp Asn Val Asp Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser 165 170 175Leu Trp Ile Ala Gly Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu 180 185 190Tyr Phe Pro Ser Met Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn 195 200 205Pro Phe Asp Lys Asn Ile Val Leu Leu Asp Asp Glu Glu Asp Asp Lys 210 215 220Pro Lys Thr Ala Gly Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe225 230 235 240Arg Arg Asn Asn Gly Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly 245 250 255Gly Val Trp Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu 260 265 270Trp Leu Lys Asp Asn Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala 275 280 285Met Ala Thr Gly Trp Val Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp 290 295 300Asp Ser Gly Ala Met Val Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp305 310 315 320Tyr Tyr Met Thr Asn Glu Arg Gly Asn Met Val Ser Asn Glu Phe Ile 325 330 335Lys Ser Gly Lys Gly Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala 340 345 350Asp Asn Pro Ser Phe Thr Lys Glu Pro Asp Gly Leu Ile Thr Val Ala 355 360 365Leu Glu His His His His His His 370 375109386PRTUnknownLL-37-Cpl1 109Met Leu Leu Gly Asp Phe Phe Arg Lys Ser Lys Glu Lys Ile Gly Lys1 5 10 15Glu Phe Lys Arg Ile Val Gln Arg Ile Lys Asp Phe Leu Arg Asn Leu 20 25 30Val Pro Arg Thr Glu Ser Gly Ser Val Lys Lys Asn Asp Leu Phe Val 35 40 45Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln 50 55 60Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr65 70 75 80Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile Gly 85 90 95Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu Arg 100 105 110Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr Leu 115 120 125Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr 130 135 140Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr Lys145 150 155 160Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp Tyr 165 170 175Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr 180 185 190Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp 195 200 205Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile 210 215 220Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr225 230 235 240Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser 245 250 255Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe 260 265 270Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu 275 280 285Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp Val 290 295 300Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met Val305 310 315 320Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu 325 330 335Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp 340 345 350Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr 355 360 365Lys Glu Pro Asp Gly Leu Ile Thr Val Ala Leu Glu His His His His 370 375 380His His385110362PRTUnknownIndolicidin-Cpl1 110Met Ile Leu Pro Trp Lys Trp Pro Trp Trp Pro Trp Arg Arg Gly Ser1 5 10 15Val Lys Lys Asn Asp Leu Phe Val Asp Val Ser Ser His Asn Gly Tyr 20 25 30Asp Ile Thr Gly Ile Leu Glu Gln Met Gly Thr Thr Asn Thr Ile Ile 35 40 45Lys Ile Ser Glu Ser Thr Thr Tyr Leu Asn Pro Cys Leu Ser Ala Gln 50 55 60Val Glu Gln Ser Asn Pro Ile Gly Phe Tyr His Phe Ala Arg Phe Gly65 70 75 80Gly Asp Val Ala Glu Ala Glu Arg Glu Ala Gln Phe Phe Leu Asp Asn 85 90 95Val Pro Met Gln Val Lys Tyr Leu Val Leu Asp Tyr Glu Asp Asp Pro 100 105 110Ser Gly Asp Ala Gln Ala Asn Thr Asn Ala Cys Leu Arg Phe Met Gln 115 120 125Met Ile Ala Asp Ala Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro 130 135 140Phe Thr His Asp Asn Val Asp Tyr Gln Gln Ile Leu Ala Gln Phe Pro145 150 155 160Asn Ser Leu Trp Ile Ala Gly Tyr Gly Leu Asn Asp Gly Thr Ala Asn 165 170 175Phe Glu Tyr Phe Pro Ser Met Asp Gly Ile Arg Trp Trp Gln Tyr Ser 180 185 190Ser Asn Pro Phe Asp Lys Asn Ile Val Leu Leu Asp Asp Glu Glu Asp 195 200 205Asp Lys Pro Lys Thr Ala Gly Thr Trp Lys Gln Asp Ser Lys Gly Trp 210 215 220Trp Phe Arg Arg Asn Asn Gly Ser Phe Pro Tyr Asn Lys Trp Glu Lys225 230 235 240Ile Gly Gly Val Trp Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys Leu Thr 245 250 255Ser Glu Trp Leu Lys Asp Asn Glu Lys Trp Tyr Tyr Leu Lys Asp Asn 260 265 270Gly Ala Met Ala Thr Gly Trp Val Leu Val Gly Ser Glu Trp Tyr Tyr 275 280 285Met Asp Asp Ser Gly Ala Met Val Thr Gly Trp Val Lys Tyr Lys Asn 290 295 300Asn Trp Tyr Tyr Met Thr Asn Glu Arg Gly Asn Met Val Ser Asn Glu305 310 315 320Phe Ile Lys Ser Gly Lys Gly Trp Tyr Phe Met Asn Thr Asn Gly Glu 325 330 335Leu Ala Asp Asn Pro Ser Phe Thr Lys Glu Pro Asp Gly Leu Ile Thr 340 345 350Val Ala Leu Glu His His His His His His 355 360111372PRTUnknownMagainin-Cpl1 111Met Gly Ile Gly Lys Phe Leu His Ser Ala Lys Lys Phe Gly Lys Ala1 5 10 15Phe Val Gly Glu Ile Met Asn Ser Gly Ser Val Lys Lys Asn Asp Leu 20 25 30Phe Val Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu 35 40 45Glu Gln Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr 50 55 60Thr Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro65 70 75 80Ile Gly Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala 85 90 95Glu Arg Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys 100 105 110Tyr Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala 115 120 125Asn Thr Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly 130 135 140Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val145 150 155 160Asp Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala 165 170 175Gly Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser 180 185 190Met Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys 195 200 205Asn Ile Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala 210 215 220Gly Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn225 230 235 240Gly Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr 245 250 255Tyr Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp 260 265 270Asn Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly 275 280 285Trp Val Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala 290 295 300Met Val Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr305 310 315 320Asn Glu Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys 325 330 335Gly Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser 340 345 350Phe Thr Lys Glu Pro Asp Gly Leu Ile Thr Val Ala Leu Glu His His 355 360 365His His His His 370112374PRTUnknownPleurocidin-Cpl1 112Met Gly Trp Gly Ser Phe Phe Lys Lys Ala Ala His Val Gly Lys His1 5 10 15Val Gly Lys Ala Ala Leu Thr His Tyr Leu Gly Ser Val Lys Lys Asn 20 25 30Asp Leu Phe Val Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly 35 40 45Ile Leu Glu Gln Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu 50 55 60Ser Thr Thr Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser65 70 75 80Asn Pro Ile Gly Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala 85 90 95Glu Ala Glu Arg Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln 100 105 110Val Lys Tyr Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala 115 120 125Gln Ala Asn Thr Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp 130 135 140Ala Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp145 150 155 160Asn Val Asp Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp 165 170 175Ile Ala Gly Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe 180 185 190Pro Ser Met Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe 195 200 205Asp Lys Asn Ile Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys 210 215 220Thr Ala Gly Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg225 230 235 240Asn Asn Gly Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val 245 250 255Trp Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu 260 265 270Lys Asp Asn Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala 275 280 285Thr Gly Trp Val Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser 290 295 300Gly Ala Met Val Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr

Tyr305 310 315 320Met Thr Asn Glu Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser 325 330 335Gly Lys Gly Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn 340 345 350Pro Ser Phe Thr Lys Glu Pro Asp Gly Leu Ile Thr Val Ala Leu Glu 355 360 365His His His His His His 370113385PRTUnknownCecropin A (A.aegypti)-Cpl1 113Met Gly Gly Leu Lys Lys Leu Gly Lys Lys Leu Glu Gly Ala Gly Lys1 5 10 15Arg Val Phe Asn Ala Ala Glu Lys Ala Leu Pro Val Val Ala Gly Ala 20 25 30Lys Ala Leu Arg Lys Gly Ser Val Lys Lys Asn Asp Leu Phe Val Asp 35 40 45Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln Met 50 55 60Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr Leu65 70 75 80Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile Gly Phe 85 90 95Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu Arg Glu 100 105 110Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr Leu Val 115 120 125Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr Asn 130 135 140Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr Lys Pro145 150 155 160Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp Tyr Gln 165 170 175Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr Gly 180 185 190Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp Gly 195 200 205Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile Val 210 215 220Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr Trp225 230 235 240Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser Phe 245 250 255Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe Asp 260 265 270Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu Lys 275 280 285Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp Val Leu 290 295 300Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met Val Thr305 310 315 320Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu Arg 325 330 335Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp Tyr 340 345 350Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr Lys 355 360 365Glu Pro Asp Gly Leu Ile Thr Val Ala Leu Glu His His His His His 370 375 380His385114370PRTUnknownBuforinII-Cpl1 114Met Thr Arg Ser Ser Arg Ala Gly Leu Gln Phe Pro Val Gly Arg Val1 5 10 15His Arg Leu Leu Arg Lys Gly Ser Val Lys Lys Asn Asp Leu Phe Val 20 25 30Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu Glu Gln 35 40 45Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr Thr Tyr 50 55 60Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro Ile Gly65 70 75 80Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala Glu Arg 85 90 95Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys Tyr Leu 100 105 110Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala Asn Thr 115 120 125Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly Tyr Lys 130 135 140Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val Asp Tyr145 150 155 160Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala Gly Tyr 165 170 175Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser Met Asp 180 185 190Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys Asn Ile 195 200 205Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala Gly Thr 210 215 220Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn Gly Ser225 230 235 240Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr Tyr Phe 245 250 255Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp Asn Glu 260 265 270Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly Trp Val 275 280 285Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala Met Val 290 295 300Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr Asn Glu305 310 315 320Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys Gly Trp 325 330 335Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser Phe Thr 340 345 350Lys Glu Pro Asp Gly Leu Ile Thr Val Ala Leu Glu His His His His 355 360 365His His 370115388PRTUnknownSarcotoxin IA-Cpl1 115Met Gly Trp Leu Lys Lys Ile Gly Lys Lys Ile Glu Arg Val Gly Gln1 5 10 15His Thr Arg Asp Ala Thr Ile Gln Gly Leu Gly Ile Ala Gln Gln Ala 20 25 30Ala Asn Val Ala Ala Thr Ala Arg Gly Ser Val Lys Lys Asn Asp Leu 35 40 45Phe Val Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly Ile Leu 50 55 60Glu Gln Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu Ser Thr65 70 75 80Thr Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser Asn Pro 85 90 95Ile Gly Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala Glu Ala 100 105 110Glu Arg Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln Val Lys 115 120 125Tyr Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala Gln Ala 130 135 140Asn Thr Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp Ala Gly145 150 155 160Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp Asn Val 165 170 175Asp Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp Ile Ala 180 185 190Gly Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe Pro Ser 195 200 205Met Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe Asp Lys 210 215 220Asn Ile Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys Thr Ala225 230 235 240Gly Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg Asn Asn 245 250 255Gly Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val Trp Tyr 260 265 270Tyr Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu Lys Asp 275 280 285Asn Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala Thr Gly 290 295 300Trp Val Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser Gly Ala305 310 315 320Met Val Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr Met Thr 325 330 335Asn Glu Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser Gly Lys 340 345 350Gly Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn Pro Ser 355 360 365Phe Thr Lys Glu Pro Asp Gly Leu Ile Thr Val Ala Leu Glu His His 370 375 380His His His His385116358PRTUnknownPK-Cpl1 116Met Lys Arg Lys Lys Arg Lys Lys Arg Lys Gly Ser Val Lys Lys Asn1 5 10 15Asp Leu Phe Val Asp Val Ser Ser His Asn Gly Tyr Asp Ile Thr Gly 20 25 30Ile Leu Glu Gln Met Gly Thr Thr Asn Thr Ile Ile Lys Ile Ser Glu 35 40 45Ser Thr Thr Tyr Leu Asn Pro Cys Leu Ser Ala Gln Val Glu Gln Ser 50 55 60Asn Pro Ile Gly Phe Tyr His Phe Ala Arg Phe Gly Gly Asp Val Ala65 70 75 80Glu Ala Glu Arg Glu Ala Gln Phe Phe Leu Asp Asn Val Pro Met Gln 85 90 95Val Lys Tyr Leu Val Leu Asp Tyr Glu Asp Asp Pro Ser Gly Asp Ala 100 105 110Gln Ala Asn Thr Asn Ala Cys Leu Arg Phe Met Gln Met Ile Ala Asp 115 120 125Ala Gly Tyr Lys Pro Ile Tyr Tyr Ser Tyr Lys Pro Phe Thr His Asp 130 135 140Asn Val Asp Tyr Gln Gln Ile Leu Ala Gln Phe Pro Asn Ser Leu Trp145 150 155 160Ile Ala Gly Tyr Gly Leu Asn Asp Gly Thr Ala Asn Phe Glu Tyr Phe 165 170 175Pro Ser Met Asp Gly Ile Arg Trp Trp Gln Tyr Ser Ser Asn Pro Phe 180 185 190Asp Lys Asn Ile Val Leu Leu Asp Asp Glu Glu Asp Asp Lys Pro Lys 195 200 205Thr Ala Gly Thr Trp Lys Gln Asp Ser Lys Gly Trp Trp Phe Arg Arg 210 215 220Asn Asn Gly Ser Phe Pro Tyr Asn Lys Trp Glu Lys Ile Gly Gly Val225 230 235 240Trp Tyr Tyr Phe Asp Ser Lys Gly Tyr Cys Leu Thr Ser Glu Trp Leu 245 250 255Lys Asp Asn Glu Lys Trp Tyr Tyr Leu Lys Asp Asn Gly Ala Met Ala 260 265 270Thr Gly Trp Val Leu Val Gly Ser Glu Trp Tyr Tyr Met Asp Asp Ser 275 280 285Gly Ala Met Val Thr Gly Trp Val Lys Tyr Lys Asn Asn Trp Tyr Tyr 290 295 300Met Thr Asn Glu Arg Gly Asn Met Val Ser Asn Glu Phe Ile Lys Ser305 310 315 320Gly Lys Gly Trp Tyr Phe Met Asn Thr Asn Gly Glu Leu Ala Asp Asn 325 330 335Pro Ser Phe Thr Lys Glu Pro Asp Gly Leu Ile Thr Val Ala Leu Glu 340 345 350His His His His His His 355117356PRTUnknownSynthetic peptide-Ply511 117Met Phe Phe Val Ala Pro Gly Ser Val Lys Tyr Thr Val Glu Asn Lys1 5 10 15Ile Ile Ala Gly Leu Pro Lys Gly Lys Leu Lys Gly Ala Asn Phe Val 20 25 30Ile Ala His Glu Thr Ala Asn Ser Lys Ser Thr Ile Asp Asn Glu Val 35 40 45Ser Tyr Met Thr Arg Asn Trp Lys Asn Ala Phe Val Thr His Phe Val 50 55 60Gly Gly Gly Gly Arg Val Val Gln Val Ala Asn Val Asn Tyr Val Ser65 70 75 80Trp Gly Ala Gly Gln Tyr Ala Asn Ser Tyr Ser Tyr Ala Gln Val Glu 85 90 95Leu Cys Arg Thr Ser Asn Ala Thr Thr Phe Lys Lys Asp Tyr Glu Val 100 105 110Tyr Cys Gln Leu Leu Val Asp Leu Ala Lys Lys Ala Gly Ile Pro Ile 115 120 125Thr Leu Asp Ser Gly Ser Lys Thr Ser Asp Lys Gly Ile Lys Ser His 130 135 140Lys Trp Val Ala Asp Lys Leu Gly Gly Thr Thr His Gln Asp Pro Tyr145 150 155 160Ala Tyr Leu Ser Ser Trp Gly Ile Ser Lys Ala Gln Phe Ala Ser Asp 165 170 175Leu Ala Lys Val Ser Gly Gly Gly Asn Thr Gly Thr Ala Pro Ala Lys 180 185 190Pro Ser Thr Pro Ala Pro Lys Pro Ser Thr Pro Ser Thr Asn Leu Asp 195 200 205Lys Leu Gly Leu Val Asp Tyr Met Asn Ala Lys Lys Met Asp Ser Ser 210 215 220Tyr Ser Asn Arg Asp Lys Leu Ala Lys Gln Tyr Gly Ile Ala Asn Tyr225 230 235 240Ser Gly Thr Ala Ser Gln Asn Thr Thr Leu Leu Ser Lys Ile Lys Gly 245 250 255Gly Ala Pro Lys Pro Ser Thr Pro Ala Pro Lys Pro Ser Thr Ser Thr 260 265 270Ala Lys Lys Ile Tyr Phe Pro Pro Asn Lys Gly Asn Trp Ser Val Tyr 275 280 285Pro Thr Asn Lys Ala Pro Val Lys Ala Asn Ala Ile Gly Ala Ile Asn 290 295 300Pro Thr Lys Phe Gly Gly Leu Thr Tyr Thr Ile Gln Lys Asp Arg Gly305 310 315 320Asn Gly Val Tyr Glu Ile Gln Thr Asp Gln Phe Gly Arg Val Gln Val 325 330 335Tyr Gly Ala Pro Ser Thr Gly Ala Val Ile Lys Lys Leu Glu His His 340 345 350His His His His 355118514PRTUnknownPK-LysK 118Met Lys Arg Lys Lys Arg Lys Lys Arg Lys Gly Ser Ala Lys Thr Gln1 5 10 15Ala Glu Ile Asn Lys Arg Leu Asp Ala Tyr Ala Lys Gly Thr Val Asp 20 25 30Ser Pro Tyr Arg Val Lys Lys Ala Thr Ser Tyr Asp Pro Ser Phe Gly 35 40 45Val Met Glu Ala Gly Ala Ile Asp Ala Asp Gly Tyr Tyr His Ala Gln 50 55 60Cys Gln Asp Leu Ile Thr Asp Tyr Val Leu Trp Leu Thr Asp Asn Lys65 70 75 80Val Arg Thr Trp Gly Asn Ala Lys Asp Gln Ile Lys Gln Ser Tyr Gly 85 90 95Thr Gly Phe Lys Ile His Glu Asn Lys Pro Ser Thr Val Pro Lys Lys 100 105 110Gly Trp Ile Ala Val Phe Thr Ser Gly Ser Tyr Glu Gln Trp Gly His 115 120 125Ile Gly Ile Val Tyr Asp Gly Gly Asn Thr Ser Thr Phe Thr Ile Leu 130 135 140Glu Gln Asn Trp Asn Gly Tyr Ala Asn Lys Lys Pro Thr Lys Arg Val145 150 155 160Asp Asn Tyr Tyr Gly Leu Thr His Phe Ile Glu Ile Pro Val Lys Ala 165 170 175Gly Thr Thr Val Lys Lys Glu Thr Ala Lys Lys Ser Ala Ser Lys Thr 180 185 190Pro Ala Pro Lys Lys Lys Ala Thr Leu Lys Val Ser Lys Asn His Ile 195 200 205Asn Tyr Thr Met Asp Lys Arg Gly Lys Lys Pro Glu Gly Met Val Ile 210 215 220His Asn Asp Ala Gly Arg Ser Ser Gly Gln Gln Tyr Glu Asn Ser Leu225 230 235 240Ala Asn Ala Gly Tyr Ala Arg Tyr Ala Asn Gly Ile Ala His Tyr Tyr 245 250 255Gly Ser Glu Gly Tyr Val Trp Glu Ala Ile Asp Ala Lys Asn Gln Ile 260 265 270Ala Trp His Thr Gly Asp Gly Thr Gly Ala Asn Ser Gly Asn Phe Arg 275 280 285Phe Ala Gly Ile Glu Val Cys Gln Ser Met Ser Ala Ser Asp Ala Gln 290 295 300Phe Leu Lys Asn Glu Gln Ala Val Phe Gln Phe Thr Ala Glu Lys Phe305 310 315 320Lys Glu Trp Gly Leu Thr Pro Asn Arg Lys Thr Val Arg Leu His Met 325 330 335Glu Phe Val Pro Thr Ala Cys Pro His Arg Ser Met Val Leu His Thr 340 345 350Gly Phe Asn Pro Val Thr Gln Gly Arg Pro Ser Gln Ala Ile Met Asn 355 360 365Lys Leu Lys Asp Tyr Phe Ile Lys Gln Ile Lys Asn Tyr Met Asp Lys 370 375 380Gly Thr Ser Ser Ser Thr Val Val Lys Asp Gly Lys Thr Ser Ser Ala385 390 395 400Ser Thr Pro Ala Thr Arg Pro Val Thr Gly Ser Trp Lys Lys Asn Gln 405 410 415Tyr Gly Thr Trp Tyr Lys Pro Glu Asn Ala Thr Phe Val Asn Gly Asn 420 425 430Gln Pro Ile Val Thr Arg Ile Gly Ser Pro Phe Leu Asn Ala Pro Val 435 440 445Gly Gly Asn Leu Pro Ala Gly Ala Thr Ile Val Tyr Asp Glu Val Cys 450 455 460Ile Gln Ala Gly His Ile Trp Ile Gly Tyr Asn Ala Tyr Asn Gly Asn465 470 475 480Arg Val Tyr Cys Pro Val Arg Thr Cys Gln Gly Val Pro Pro Asn Gln 485 490 495Ile Pro Gly Val Ala Trp Gly Val Phe Lys Leu Glu His His His His 500 505 510His His119272PRTUnknownPK-Lss 119Ala Met Gly Lys Arg Lys Lys Arg Lys Lys Arg Lys Gly Ser Ala His1 5

10 15Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys Lys Gly Tyr Gly Tyr 20 25 30Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met His Tyr Gly Val Asp 35 40 45Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala Ile Ser Ser Gly Lys 50 55 60Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly Gly Asn Gln Ile Gly65 70 75 80Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp Tyr Met His Leu Ser 85 90 95Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys Ala Gly Gln Ile Ile 100 105 110Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala Pro His Leu His Phe 115 120 125Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr Ala Gln Asp Pro Met 130 135 140Pro Phe Leu Lys Ser Ala Gly Tyr Gly Lys Ala Gly Gly Thr Val Thr145 150 155 160Pro Thr Pro Asn Thr Gly Trp Lys Thr Asn Lys Tyr Gly Thr Leu Tyr 165 170 175Lys Ser Glu Ser Ala Ser Phe Thr Pro Asn Thr Asp Ile Ile Thr Arg 180 185 190Thr Thr Gly Pro Phe Arg Ser Met Pro Gln Ser Gly Val Leu Lys Ala 195 200 205Gly Gln Thr Ile His Tyr Asp Glu Val Met Lys Gln Asp Gly His Val 210 215 220Trp Val Gly Tyr Thr Gly Asn Ser Gly Gln Arg Ile Tyr Leu Pro Val225 230 235 240Arg Thr Trp Asn Lys Ser Thr Asn Thr Leu Gly Val Leu Trp Gly Thr 245 250 255Ile Lys Leu Val Pro Arg Gly Ser Leu Glu His His His His His His 260 265 270120281PRTUnknownPK2-Lss 120Ala Met Gly Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys Arg Lys Lys1 5 10 15Arg Lys Lys Arg Lys Gly Ser Ala His Glu His Ser Ala Gln Trp Leu 20 25 30Asn Asn Tyr Lys Lys Gly Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile 35 40 45Asn Gly Gly Met His Tyr Gly Val Asp Phe Phe Met Asn Ile Gly Thr 50 55 60Pro Val Lys Ala Ile Ser Ser Gly Lys Ile Val Glu Ala Gly Trp Ser65 70 75 80Asn Tyr Gly Gly Gly Asn Gln Ile Gly Leu Ile Glu Asn Asp Gly Val 85 90 95His Arg Gln Trp Tyr Met His Leu Ser Lys Tyr Asn Val Lys Val Gly 100 105 110Asp Tyr Val Lys Ala Gly Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly 115 120 125Tyr Ser Thr Ala Pro His Leu His Phe Gln Arg Met Val Asn Ser Phe 130 135 140Ser Asn Ser Thr Ala Gln Asp Pro Met Pro Phe Leu Lys Ser Ala Gly145 150 155 160Tyr Gly Lys Ala Gly Gly Thr Val Thr Pro Thr Pro Asn Thr Gly Trp 165 170 175Lys Thr Asn Lys Tyr Gly Thr Leu Tyr Lys Ser Glu Ser Ala Ser Phe 180 185 190Thr Pro Asn Thr Asp Ile Ile Thr Arg Thr Thr Gly Pro Phe Arg Ser 195 200 205Met Pro Gln Ser Gly Val Leu Lys Ala Gly Gln Thr Ile His Tyr Asp 210 215 220Glu Val Met Lys Gln Asp Gly His Val Trp Val Gly Tyr Thr Gly Asn225 230 235 240Ser Gly Gln Arg Ile Tyr Leu Pro Val Arg Thr Trp Asn Lys Ser Thr 245 250 255Asn Thr Leu Gly Val Leu Trp Gly Thr Ile Lys Leu Val Pro Arg Gly 260 265 270Ser Leu Glu His His His His His His 275 280121525PRTUnknownLysK-PK (PK C-terminal) 121Met Gly Ser Ser His His His His His His Ser Ser Gly Leu Val Pro1 5 10 15Arg Gly Ser His Met Ala Lys Thr Gln Ala Glu Ile Asn Lys Arg Leu 20 25 30Asp Ala Tyr Ala Lys Gly Thr Val Asp Ser Pro Tyr Arg Val Lys Lys 35 40 45Ala Thr Ser Tyr Asp Pro Ser Phe Gly Val Met Glu Ala Gly Ala Ile 50 55 60Asp Ala Asp Gly Tyr Tyr His Ala Gln Cys Gln Asp Leu Ile Thr Asp65 70 75 80Tyr Val Leu Trp Leu Thr Asp Asn Lys Val Arg Thr Trp Gly Asn Ala 85 90 95Lys Asp Gln Ile Lys Gln Ser Tyr Gly Thr Gly Phe Lys Ile His Glu 100 105 110Asn Lys Pro Ser Thr Val Pro Lys Lys Gly Trp Ile Ala Val Phe Thr 115 120 125Ser Gly Ser Tyr Glu Gln Trp Gly His Ile Gly Ile Val Tyr Asp Gly 130 135 140Gly Asn Thr Ser Thr Phe Thr Ile Leu Glu Gln Asn Trp Asn Gly Tyr145 150 155 160Ala Asn Lys Lys Pro Thr Lys Arg Val Asp Asn Tyr Tyr Gly Leu Thr 165 170 175His Phe Ile Glu Ile Pro Val Lys Ala Gly Thr Thr Val Lys Lys Glu 180 185 190Thr Ala Lys Lys Ser Ala Ser Lys Thr Pro Ala Pro Lys Lys Lys Ala 195 200 205Thr Leu Lys Val Ser Lys Asn His Ile Asn Tyr Thr Met Asp Lys Arg 210 215 220Gly Lys Lys Pro Glu Gly Met Val Ile His Asn Asp Ala Gly Arg Ser225 230 235 240Ser Gly Gln Gln Tyr Glu Asn Ser Leu Ala Asn Ala Gly Tyr Ala Arg 245 250 255Tyr Ala Asn Gly Ile Ala His Tyr Tyr Gly Ser Glu Gly Tyr Val Trp 260 265 270Glu Ala Ile Asp Ala Lys Asn Gln Ile Ala Trp His Thr Gly Asp Gly 275 280 285Thr Gly Ala Asn Ser Gly Asn Phe Arg Phe Ala Gly Ile Glu Val Cys 290 295 300Gln Ser Met Ser Ala Ser Asp Ala Gln Phe Leu Lys Asn Glu Gln Ala305 310 315 320Val Phe Gln Phe Thr Ala Glu Lys Phe Lys Glu Trp Gly Leu Thr Pro 325 330 335Asn Arg Lys Thr Val Arg Leu His Met Glu Phe Val Pro Thr Ala Cys 340 345 350Pro His Arg Ser Met Val Leu His Thr Gly Phe Asn Pro Val Thr Gln 355 360 365Gly Arg Pro Ser Gln Ala Ile Met Asn Lys Leu Lys Asp Tyr Phe Ile 370 375 380Lys Gln Ile Lys Asn Tyr Met Asp Lys Gly Thr Ser Ser Ser Thr Val385 390 395 400Val Lys Asp Gly Lys Thr Ser Ser Ala Ser Thr Pro Ala Thr Arg Pro 405 410 415Val Thr Gly Ser Trp Lys Lys Asn Gln Tyr Gly Thr Trp Tyr Lys Pro 420 425 430Glu Asn Ala Thr Phe Val Asn Gly Asn Gln Pro Ile Val Thr Arg Ile 435 440 445Gly Ser Pro Phe Leu Asn Ala Pro Val Gly Gly Asn Leu Pro Ala Gly 450 455 460Ala Thr Ile Val Tyr Asp Glu Val Cys Ile Gln Ala Gly His Ile Trp465 470 475 480Ile Gly Tyr Asn Ala Tyr Asn Gly Asn Arg Val Tyr Cys Pro Val Arg 485 490 495Thr Cys Gln Gly Val Pro Pro Asn Gln Ile Pro Gly Val Ala Trp Gly 500 505 510Val Phe Lys Ser Lys Arg Lys Lys Arg Lys Lys Arg Lys 515 520 525122274PRTUnknownLss-PK (PK C-terminal) 122Met Gly Ser Ser His His His His His His Ser Ser Gly Leu Val Pro1 5 10 15Arg Gly Ser His Met His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr 20 25 30Lys Lys Gly Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly 35 40 45Met His Tyr Gly Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys 50 55 60Ala Ile Ser Ser Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly65 70 75 80Gly Gly Asn Gln Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln 85 90 95Trp Tyr Met His Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val 100 105 110Lys Ala Gly Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr 115 120 125Ala Pro His Leu His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser 130 135 140Thr Ala Gln Asp Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Lys145 150 155 160Ala Gly Gly Thr Val Thr Pro Thr Pro Asn Thr Gly Trp Lys Thr Asn 165 170 175Lys Tyr Gly Thr Leu Tyr Lys Ser Glu Ser Ala Ser Phe Thr Pro Asn 180 185 190Thr Asp Ile Ile Thr Arg Thr Thr Gly Pro Phe Arg Ser Met Pro Gln 195 200 205Ser Gly Val Leu Lys Ala Gly Gln Thr Ile His Tyr Asp Glu Val Met 210 215 220Lys Gln Asp Gly His Val Trp Val Gly Tyr Thr Gly Asn Ser Gly Gln225 230 235 240Arg Ile Tyr Leu Pro Val Arg Thr Trp Asn Lys Ser Thr Asn Thr Leu 245 250 255Gly Val Leu Trp Gly Thr Ile Lys Ser Lys Arg Lys Lys Arg Lys Lys 260 265 270Arg Lys123858DNAunknownPA6gp20 123atggtacgct acatcccagc agcgcatcac tctgcaggct ctaacaaccc ggtgaaccgt 60gtagtgatcc acgcgacctg tccggatgta ggcttcccgt ctgcttcccg taaaggtcgt 120gcggtttcca ctgcgaacta cttcgcgtct ccgtcctctg gcggttctgc acactacgtg 180tgcgatatcg gtgagaccgt gcagtgcctg tccgaaagca ctattggttg gcacgctccg 240ccgaacccac atagcctggg tatcgaaatc tgtgctgacg gtggctccca cgcttctttc 300cgtgtcccag gtcacgctta cactcgcgaa cagtggctgg atccacaggt ttggccagcc 360gtagaacgtg ctgcagttct gtgtcgtcgc ctgtgcgaca aatataacgt cccgaaacgc 420aaactgtctg cagcggacct gaaagcaggt cgtcgtggtg tttgcggtca cgttgacgta 480accgacgcct ggcaccagtc tgatcacgac gatccgggtc cgtggtttcc gtgggacaaa 540ttcatggcag tggttaacgg tggcagcggt gattctggcg aactgaccgt tgccgacgtc 600aaagcgctgc acgaccagat taaacagctc tctgctcagc tgaccggtag cgtgaacaaa 660ctgcaccatg acgtaggcgt tgtccaggtt cagaacggtg atctgggcaa acgcgttgat 720gctctgagct gggtgaaaaa cccggtgacg ggtaaactgt ggcgtaccaa agatgcgctg 780tggtccgttt ggtactatgt tctggaatgc cgtagccgtc tggaccgtct ggaatctgcc 840gtgaacgacc tgaaaaaa 858124314PRTunknownWalmagh1-PA6gp20 124Met Gly Phe Phe Ile Pro Ala Val Ile Leu Pro Ser Ile Ala Phe Leu1 5 10 15Ile Val Pro Gly Ser Val Arg Tyr Ile Pro Ala Ala His His Ser Ala 20 25 30Gly Ser Asn Asn Pro Val Asn Arg Val Val Ile His Ala Thr Cys Pro 35 40 45Asp Val Gly Phe Pro Ser Ala Ser Arg Lys Gly Arg Ala Val Ser Thr 50 55 60Ala Asn Tyr Phe Ala Ser Pro Ser Ser Gly Gly Ser Ala His Tyr Val65 70 75 80Cys Asp Ile Gly Glu Thr Val Gln Cys Leu Ser Glu Ser Thr Ile Gly 85 90 95Trp His Ala Pro Pro Asn Pro His Ser Leu Gly Ile Glu Ile Cys Ala 100 105 110Asp Gly Gly Ser His Ala Ser Phe Arg Val Pro Gly His Ala Tyr Thr 115 120 125Arg Glu Gln Trp Leu Asp Pro Gln Val Trp Pro Ala Val Glu Arg Ala 130 135 140Ala Val Leu Cys Arg Arg Leu Cys Asp Lys Tyr Asn Val Pro Lys Arg145 150 155 160Lys Leu Ser Ala Ala Asp Leu Lys Ala Gly Arg Arg Gly Val Cys Gly 165 170 175His Val Asp Val Thr Asp Ala Trp His Gln Ser Asp His Asp Asp Pro 180 185 190Gly Pro Trp Phe Pro Trp Asp Lys Phe Met Ala Val Val Asn Gly Gly 195 200 205Ser Gly Asp Ser Gly Glu Leu Thr Val Ala Asp Val Lys Ala Leu His 210 215 220Asp Gln Ile Lys Gln Leu Ser Ala Gln Leu Thr Gly Ser Val Asn Lys225 230 235 240Leu His His Asp Val Gly Val Val Gln Val Gln Asn Gly Asp Leu Gly 245 250 255Lys Arg Val Asp Ala Leu Ser Trp Val Lys Asn Pro Val Thr Gly Lys 260 265 270Leu Trp Arg Thr Lys Asp Ala Leu Trp Ser Val Trp Tyr Tyr Val Leu 275 280 285Glu Cys Arg Ser Arg Leu Asp Arg Leu Glu Ser Ala Val Asn Asp Leu 290 295 300Lys Lys Leu Glu His His His His His His305 310

Claims

1. A fusion protein comprising an enzyme having Gram-positive cell wall degrading activity and a peptide segment fused to the enzyme at the N- or C-terminus or at both termini.

2. The fusion protein according to claim 1, wherein said fusion protein comprises an additional amino acid residue on the N-terminus.

3. The fusion protein according to claim 1, wherein said fusion protein exhibits an amino acid sequence according to SEQ ID NO: 63 to 90.

4. The fusion protein according to claim 1, wherein said fusion protein comprises a tag or additional protein on the C- and/or N-terminus.

5. The fusion protein according to claim 4, wherein said tag or additional protein is linked to the fusion protein by one or more additional amino acid residues.

6. The fusion protein according to any of the preceding claims, wherein the peptide segment is linked to the fusion protein by one or more additional amino acid residues.

7. The fusion protein according to claim 1, wherein the enzyme is an endolysin, autolysin or a bacteriocin.

8. The fusion protein according to claim 7, wherein the enzyme exhibits an amino acid sequence according to SEQ ID NO: 57 to 61.

9. The fusion protein according to claim 1, wherein the Gram-positive cell wall degrading activity is against a bacterium selected from the group consisting of the bacteria listed in Table 1.

10. The fusion protein according to claim 1, wherein the peptide segment is a cationic.

11. The fusion protein according to claim 32, wherein the sushi peptide exhibits an amino acid sequence according to SEQ ID NO: 54.

12. The fusion protein according to claim 10, wherein the cationic peptide comprises at least one amino acid residue selected out of the group consisting of arginine, histidine and lysine residues.

13. The fusion protein according to claim 32, wherein the antimicrobial peptide exhibits an amino acid sequence according to SEQ ID NO:1 to 11 or 48 to 53.

14. The fusion protein according to claim 32, wherein the hydrophobic peptide exhibits an amino acid sequence according to SEQ ID NO: 12, 50, 55 or 56.

15. The fusion protein according to claim 10, wherein at least about 70% of the amino acid residues of said cationic peptide are either arginine, histidine or lysine residues, or wherein at least about 70% of the amino acid residues of said peptide are either arginine or lysine, or wherein the amino acid residues of said peptide are either arginine or lysine residues.

16. The fusion protein according to claim 15, wherein the cationic peptide exhibits an amino acid sequence according to SEQ ID NO: 13 or 24 to 44.

17. The fusion protein according to claim 32, wherein the amphipatic peptide comprises at least one positively charged amino acid residue selected from the group consisting of lysine, arginine and histidine residues, and is combined with at least one hydrophobic amino acid residue selected from the group consisting of valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, cysteine, alanine, tyrosine, histidine, threonin, serine, proline and glycine residues.

18. The fusion protein according to claim 17, wherein at least about 70% of the amino acid residues in said amphipatic peptide are either arginine or lysine residues and at least about 30% of the amino acid residues in said amphipatic peptide are valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, cysteine, alanine, tyrosine, histidine, threonin, serine, proline or glycine residues.

19. The fusion protein according to claim 18, wherein the amphipatic peptide exhibits an amino acid sequence according to SEQ ID NO: 1 to 5, 23, 48 or 49.

20. The fusion protein according to claim 1, wherein the peptide segment comprises about 5 to about 100 amino acid residues.

21. An isolated nucleic acid molecule encoding a fusion protein according to claim 1.

22. A vector comprising a nucleic acid molecule encoding a fusion protein according to claim 1.

23. A host cell comprising a nucleic acid molecule encoding a nucleic acid according to claim 1.

24. The host cell according to claim 23, wherein the cell is a bacterial cell or a yeast cell.

25. The host cell according to claim 24, wherein the yeast cell is Pichia pastoris cell.

26. A method of treating or diagnosing a disease or condition comprising contacting a subject or sample with a fusion protein according claim 1.

27. The method of claim 26, wherein said disease is a Gram-positive bacterial infection.

28. A method for disinfecting a surface or article comprising contacting said surface or article with a fusion protein according to claim 1.

29. A method of treating or preventing Gram-positive bacterial contamination of a foodstuff, a food processing equipment, a food processing plant, a surface coming into contact with foodstuff, a medical device, of or a surface or surgical field in a hospital comprising contacting a said foodstuff, equipment, plant, surface, device or surgical field with the fusion protein according to claim 1.

30. method for diagnosing and infection or condition in medicine, food, feed or an environment comprising contacting a sample of said medicine, food, feed or environment with the fusion protein according to claim 1.

31. A pharmaceutical composition comprising a fusion protein according to claim 1.

32. The fusion protein according to claim 10, wherein the cationic peptide segment is a polycationic peptide, amphipatic peptide, sushi peptide, defensin, hydrophobic peptide or an antimicrobial peptide.

33. The fusion protein of claim 20, wherein the peptide segment comprises about 5 to 50 amino acid residues.

34. The fusion protein of claim 20, wherein the peptide segment comprises about 5 to 30 amino acid residues.

Images