Method for preparing protein shaped body

Abstract

The object of the present invention is to provide a method for preparing a protein molded body, which can not only maintain sufficient strength but also solve the problems caused by the esterification of hydroxyl groups contained in the protein. The method for preparing a protein molded body of the present invention includes a step of hydrolyzing the ester group by bringing a raw material molded body containing a protein with esterified hydroxyl groups into contact with an acidic or alkaline medium under a tensile force.

Description

Technical Field

[0001] The present invention relates to a method for preparing a protein shaped body. Background Art

[0002] Unlike synthetic fibers derived from petroleum, protein fibers such as silk are highly biodegradable. Therefore, with environmental concerns increasing in recent years, they are expected to be used as an alternative to synthetic fibers in various applications. One method for producing protein fibers is spinning using acids such as formic acid. For example, Patent Document 1 discloses a method for treating biological samples containing structured polypeptides with an acid.

[0003] Prior art literature

[0004] Patent Literature

[0005] Patent Document 1: Japanese Patent Application No. 2004-503204 Summary of the Invention

[0006] Problems to be solved by the invention

[0007] The present inventors have discovered that protein fibers prepared using a doping solution (spinning solution) with carboxylic acids such as formic acid as a solvent form ester groups during the spinning process through a dehydration condensation reaction between hydroxyl groups in the protein and carboxylic acids. The present inventors have also discovered that in protein fibers obtained by this method, the ester groups added to the protein are sometimes hydrolyzed using trace amounts of carboxylic acids such as formic acid remaining on the surface or inside the protein as a catalyst, thereby freeing the carboxylic acids, which can cause malodors, etc. According to the present inventors' research on this issue, it is known that by contacting the protein with esterified hydroxyl groups with an acidic or alkaline medium to hydrolyze the ester groups, it is possible to remove or reduce the ester groups that cause malodors, etc.

[0008] As described above, protein fibers and other protein shaped articles are expected to be used in a variety of applications and, therefore, are expected to have sufficient strength for certain applications. However, sufficient strength cannot be achieved simply by exposing proteins with esterified hydroxyl groups to an acidic or alkaline medium to hydrolyze the ester groups. The present invention aims to address this newly discovered problem.

[0009] Specifically, the present invention aims to provide a method for preparing a protein shaped article that not only maintains sufficient strength but also solves problems arising from the esterification of hydroxyl groups contained in the protein. Furthermore, the present invention aims to provide a method for processing a protein shaped article that not only maintains sufficient strength but also solves problems arising from the esterification of hydroxyl groups contained in the protein.

[0010] Methods used to solve problems

[0011] The present invention relates to, for example, the following inventions. [1]

[0013] A method for producing a protein shaped body comprises the step of hydrolyzing the ester groups by bringing a raw material shaped body containing a protein in which hydroxyl groups are esterified into contact with an acidic or alkaline medium while applying tension. [2]

[0015] The method for producing a protein molded product as described in [1], wherein the medium is an aqueous solution. [3]

[0017] The method for producing a protein molded product as described in [2], wherein the aqueous solution is an alkaline aqueous solution with a pH value of less than 12. [4]

[0019] The method for producing a protein molded body according to [2] or [3], wherein the tensile force is such that the raw material molded body does not shrink due to contact with the aqueous solution. [5]

[0021] The method for producing a protein shaped body according to any one of [1] to [4], wherein the protein is a structural protein. [6]

[0023] The method for producing a protein molded body as described in [5], wherein the structural protein is fibroin. [7]

[0025] The method for producing a protein molded product as described in [6], wherein the silk fibroin is spider silk fibroin. [8]

[0027] The method for producing a protein shaped product according to any one of [1] to [7], wherein the protein in which the hydroxyl group is esterified contains a formate ester. [9]

[0029] The method for producing a protein shaped body according to any one of [1] to [8], wherein the raw material shaped body is at least one selected from the group consisting of fibers, heated and pressed shaped bodies, films, porous bodies, gels, and resins.

[10]

[0031] A method for processing a protein shaped body comprises the step of hydrolyzing the ester groups by bringing the shaped body containing a protein having esterified hydroxyl groups into contact with an acidic or alkaline medium while applying tension.

[0032] Effects of the Invention

[0033] The present invention provides a method for preparing a protein shaped article that not only maintains sufficient strength but also solves problems arising from the esterification of hydroxyl groups contained in the protein. Furthermore, the present invention provides a method for processing a protein shaped article that not only maintains sufficient strength but also solves problems arising from the esterification of hydroxyl groups contained in the protein. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is a schematic diagram showing an example of the domain sequence of modified fibroin.

[0035] Figure 2 This is a schematic diagram showing an example of the domain sequence of modified fibroin.

[0036] Figure 3 This is a schematic diagram showing an example of the domain sequence of modified fibroin.

[0037] Figure 4 FT-IR spectra of protein fiber before and after ester hydrolysis (1730cm -1 : Peak based on ester C═O).

[0038] Figure 5 It is a graph showing a stress (vertical axis)-elongation (horizontal axis) curve in elongation evaluation. DETAILED DESCRIPTION

[0039] Hereinafter, specific embodiments of the present invention will be described in detail. However, the present invention is not limited to any of the following embodiments.

[0040] (Method for preparing protein molded product)

[0041] The method for producing a protein shaped body according to this embodiment includes the step of hydrolyzing the ester groups by bringing a raw material shaped body containing a protein having esterified hydroxyl groups into contact with an acidic or alkaline medium while applying tension.

[0042] In the present embodiment, the raw material molded body may be at least one selected from the group consisting of fibers, heat-pressed molded bodies, films, porous bodies, gels, and resins.

[0043] In this embodiment, the raw material molded article comprises a protein in which a hydroxyl group is esterified. As used herein, "hydroxyl-esterified protein" refers to a protein containing an ester group formed by ester bonds between a hydroxyl group of the protein and a carboxylic acid. The hydroxyl-esterified protein may contain formate, acetate, propionate, or the like, preferably formate.

[0044] (protein)

[0045] The protein described in this embodiment (hereinafter also referred to as the "target protein") can be, for example, a structural protein. A structural protein refers to a protein that forms an active structure or a protein derived therefrom. Specifically, the structural protein can be a naturally occurring structural protein, or a modified protein in which a portion of the amino acid sequence of a naturally occurring structural protein (e.g., less than 10% of the amino acid sequence) has been modified.

[0046] Examples of structural proteins include silk fibroin, collagen, lecithin, elastin, keratin, and proteins derived therefrom. Silk fibroin, for example, may be one or more selected from silk fibroin, spider silk fibroin, and bee silk fibroin. The structural protein may be silk fibroin, spider silk fibroin, or a combination thereof.

[0047] Silk fibroin includes naturally derived silk fibroin and modified silk fibroin. In this specification, "naturally derived silk fibroin" refers to silk fibroin having the same amino acid sequence as naturally derived silk fibroin, and "modified silk fibroin" refers to silk fibroin having an amino acid sequence different from naturally derived silk fibroin.

[0048] The silk fibroin is preferably spider silk fibroin. Spider silk fibroin includes natural spider silk fibroin and modified fibroin derived from natural spider silk fibroin. As natural spider silk fibroin, for example, spider silk protein produced by spiders can be cited.

[0049] For example, fibroin can be exemplified by the formula 1: [(A) n motif-REP1] m Or formula 2: [(A) n motif-REP1] m -(A) n A protein having a domain sequence represented by a motif. Silk fibroin may further have an amino acid sequence (N-terminal sequence and C-terminal sequence) added to either or both of the N-terminal and C-terminal ends of the domain sequence. The N-terminal and C-terminal sequences are not limited thereto and are typically regions of silk fibroin that do not have a characteristic amino acid motif repeat and are composed of approximately 100 amino acid residues.

[0050] In this specification, "domain sequence" is a crystallization region that generates fibroin (usually equivalent to the amino acid sequence (A) n motif) and an amino acid sequence of an amorphous region (usually equivalent to the REP of an amino acid sequence) is represented by the formula 1: [(A) n motif-REP] m Or formula 2: [(A) n motif-REP] m-(A) n The amino acid sequence shown in the motif. Here, (A) n The motif represents an amino acid sequence mainly composed of alanine residues, with the number of amino acid residues ranging from 2 to 27. (A) n The number of amino acid residues in the motif may be an integer of 2 to 20, 4 to 27, 4 to 20, 8 to 20, 10 to 20, 4 to 16, 8 to 16, or 10 to 16. In addition, as long as (A) n The ratio of the number of alanine residues in the motif to the total number of amino acid residues is sufficient to be 40% or more, and may be 60% or more, 70% or more, 80% or more, 83% or more, 85% or more, 86% or more, 90% or more, 95% or more, or 100% (meaning that it is composed only of alanine residues). n At least 7 of the motifs may be composed of only alanine residues. REP represents an amino acid sequence composed of 2 to 200 amino acid residues. REP may be an amino acid sequence composed of 10 to 200 amino acid residues. m represents an integer of 2 to 300, or an integer of 10 to 300. The presence of multiple (A) n The motifs may be the same amino acid sequence or different amino acid sequences. The multiple REPs may be the same amino acid sequence or different amino acid sequences.

[0051] For example, the gene sequence of the naturally derived silk fibroin obtained by cloning can be modified by, for example, modifying the amino acid sequence by substitution, deletion, insertion, and / or addition of one or more amino acid residues. The substitution, deletion, insertion, and / or addition of amino acid residues can be performed by methods well known to those skilled in the art, such as local specific mutagenesis. Specifically, it can be performed according to the methods described in the literature such as Nucleic Acid Res. 10, 6487 (1982) and Methods in Enzymology, 100, 448 (1983).

[0052] The natural source of silk fibroin comprises formula 1: [(A) n motif-REP] m Or formula 2: [(A) n motif-REP] m -(A) n Specific examples of proteins having a domain sequence represented by the motif include silk fibroin produced by insects or spiders.

[0053] Examples of silk fibroin produced by insects include silk fibroin produced by silkworms such as the domesticated silkworm (Bombyx mori), the wild silkworm (Bombyx mandarina), the silkworm (Antheraea yamamai), the tussah (Anteraea pernyi), the maple silkworm (Eriogyna pyretorum), the castor silkworm (Pilosamia Cynthia ricini), the caterpillar silkworm (Samia cynthia), the camphor silkworm (Caligura japonica), the Indian tussah (Antheraea mylitta), and the amber silkworm (Antheraea assama); and bee silk fibroin produced by the larvae of the sparrow bee (Vespa simillima xanthoptera).

[0054] More specific examples of silk fibroin produced by insects include, for example, silkworm silk fibroin L chain (GenBank accession numbers M76430 (base sequence) and AAA27840.1 (amino acid sequence)).

[0055] Examples of the silk core proteins produced by spiders include spiders belonging to the genus Araneus, such as Araneus spp., Araneus spp., Araneus spp., Araneus spp., Araneus spp., and Araneus nojimai; spiders belonging to the genus Neoscona, such as Araneus spp., Araneus spp., and Araneus spp.; spiders belonging to the genus Pronus, such as Araneus spp.; spiders belonging to the genus Cyrtarachne, such as Araneus spp. and Araneus spp.; spiders belonging to the genus Gasteracantha, such as Araneus spp. and Araneus spp.; spiders belonging to the genus Hesperus spp. and Hexapoda spp. Spiders belonging to the genus Ordgarius, such as the abdominal spider, spiders belonging to the genus Argiope, such as the pleasant-eyed spider, spider with small pleasant eyes and spider with horizontal stripes, spiders belonging to the genus Arachnura, such as the double-peaked garden spider, spiders belonging to the genus Acusilas, such as the brown hanging leaf spider, spiders belonging to the genus Cytophora, such as the red clouded spider, flower clouded spider and full-color clouded spider, spiders belonging to the genus Poltys, such as the ugly cone-headed spider, and eight-headed spiders. Spider silk proteins produced by spiders belonging to the genus Cyclosa, such as the knob-shaped spider, the four-lobed spider, the round-bellied spider, and the black-tailed spider, and spiders belonging to the genus Chorizops, such as the Japanese strong-headed spider, as well as spiders belonging to the genus Tetragnatha, such as the anterior-toothed spider, the cone-bellied spider, the straight-stretched spider, and the scale-marked spider, belonging to the genus Leucauge, and spiders belonging to the genus Nephila, such as the clavate astilbe and the spotted astilbe, belonging to the genus Nephila. Spiders belonging to the genus Nephila, spiders belonging to the genus Menosira such as the beautiful spider, spiders belonging to the genus Dyschiriognatha such as the delicate spider, spiders belonging to the genus Latrodectus such as the red-spotted spider, spiders belonging to the genus Haus, spiders belonging to the genus Geometric, and spiders belonging to the genus Interspotted, and spiders belonging to the family Tetragnathidae such as spiders belonging to the genus Euprosthenops. Examples of spider silk proteins include dragline silk proteins such as MaSp (MaSp1 and MaSp2) and ADF (ADF3 and ADF4), and MiSp (MiSp1 and MiSp2).

[0056] More specific examples of spider silk proteins produced by spiders include fibroin-3 (adf-3) [derived from Araneus diadematus] (GenBank Accession No. AAC47010 (amino acid sequence), U47855 (base sequence)), fibroin-4 (adf-4) [derived from Araneus diadematus] (GenBank Accession No. AAC47011 (amino acid sequence), U47856 (base sequence)), dragline silk protein spidroin 1 [derived from Nephila clavipes] (GenBank Accession No. AAC04504 (amino acid sequence), U37520 (base sequence)), major ampullate spidroin 1 [derived from Latrodectus hesperus] (GenBank Accession No. ABR68856 (amino acid sequence), EF595246 (base sequence)), dragline silk protein spidroin 2 [derived from Nephila clavata] (GenBank Accession Nos. AAL32472 (amino acid sequence), AF441245 (base sequence)), major ampullate spidroin 1 [from Euprosthenops australis] (GenBank Accession Nos. CAJ00428 (amino acid sequence), AJ973155 (base sequence)), and major ampullate spidroin 2 [Euprosthenops australis] (GenBank Accession Nos. CAM32249.1 (amino acid sequence), AM490169 (base sequence)), minor ampullate silk protein 1 [Nephila clavipes] (GenBank Accession No. AAC14589.1 (amino acid sequence)), minor ampullate silk protein 2 [Nephila clavipes] (GenBank Accession No. AAC14591.1 (amino acid sequence)), minor ampullate spidroin-like protein [Nephila clavipes] cruentata] (GenBank accession number ABR37278.1 (amino acid sequence), etc.

[0057] As a more specific example of naturally derived silk fibroin, further examples include silk fibroin for which sequence information is registered in NCBI GenBank. For example, identification can be achieved by extracting sequences containing the classification code "INV" (division) in the sequence information registered in NCBI GenBank, where the keywords "spidroin," "ampullar gland," "fibroin," "silk and polypeptide," or "silk and protein" are listed in the definition (DEFINITION), extracting the character string specifying the product from the CDS, and extracting the sequence containing the specified character string in the tissue type (TISSUE TYPE) from the source (SOURCE).

[0058] The modified silk fibroin can be modified silk fibroin (a silk fibroin produced by a silkworm with a modified amino acid sequence) or modified spider silk fibroin (a silk fibroin produced by a spider with a modified amino acid sequence). Modified spider silk fibroin is preferred.

[0059] Specific examples of modified silk fibroin include modified silk fibroin derived from the large silk tube dragline protein produced by the spider ampullate gland (first modified silk fibroin), modified silk fibroin having a domain sequence with a reduced content of glycine residues (second modified silk fibroin), and modified silk fibroin having (A) n Modified silk fibroin with a domain sequence having reduced motif content (the third modified silk fibroin), glycine residue content and (A) n A modified silk fibroin with reduced motif content (the 4th modified silk fibroin), a modified silk fibroin having a domain sequence containing a local large hydrophobicity index region (the 5th modified silk fibroin), and a modified silk fibroin having a domain sequence with reduced glutamine residue content (the 6th modified silk fibroin).

[0060] The first modified silk fibroin may include a silk fibroin comprising the formula 1: [(A) n motif-REP] m In the first modified silk fibroin, (A) n The number of amino acid residues in the motif is preferably an integer from 3 to 20, more preferably an integer from 4 to 20, further preferably an integer from 8 to 20, further preferably an integer from 10 to 20, further preferably an integer from 4 to 16, particularly preferably an integer from 8 to 16, and most preferably an integer from 10 to 16. In the first modified fibroin, the number of amino acid residues constituting REP in Formula 1 is preferably 10 to 200 residues, more preferably 10 to 150 residues, further preferably 20 to 100 residues, and further preferably 20 to 75 residues. In the first modified fibroin, Formula 1: [(A)n motif-REP] m The total number of glycine residues, serine residues, and alanine residues contained in the amino acid sequence is preferably 40% or more, more preferably 60% or more, and even more preferably 70% or more relative to the total number of amino acid residues.

[0061] The first modified silk fibroin may be the following polypeptide, which comprises Formula 1: [(A) n motif-REP] m The amino acid sequence is a unit of SEQ ID NOs: 1 to 3, and the C-terminal sequence is an amino acid sequence shown in any one of SEQ ID NOs: 1 to 3, or an amino acid sequence having 90% or more identity with the amino acid sequence shown in any one of SEQ ID NOs: 1 to 3.

[0062] The amino acid sequence shown in sequence number 1 is identical to the amino acid sequence consisting of the 50 amino acid residues at the C-terminus of the amino acid sequence of ADF3 (GI: 1263287, NCBI), the amino acid sequence shown in sequence number 2 is identical to the amino acid sequence after removing 20 residues from the C-terminus of the amino acid sequence shown in sequence number 1, and the amino acid sequence shown in sequence number 3 is identical to the amino acid sequence after removing 29 residues from the C-terminus of the amino acid sequence shown in sequence number 1.

[0063] More specific examples of the first modified silk fibroin include modified silk fibroin comprising an amino acid sequence having 90% or greater sequence identity with the amino acid sequence set forth in (1-i) SEQ ID NO: 4 (recombinant spider silk protein ADF3KaiLargeNRSH1) or the amino acid sequence set forth in (1-ii) SEQ ID NO: 4. The sequence identity is preferably 95% or greater.

[0064] The amino acid sequence set forth in SEQ ID NO: 4 is derived from the amino acid sequence of ADF3, to which an amino acid sequence (SEQ ID NO: 5) consisting of a start codon, a His10 tag, and an HRV3C protease (Human rhinovirus 3C protease) recognition site is added at the N-terminus. The amino acid sequence is mutated to increase the repeat region at positions 1 to 13 by approximately twofold and terminate translation at amino acid residue 1154. The amino acid sequence at the C-terminus of the amino acid sequence set forth in SEQ ID NO: 4 is identical to the amino acid sequence set forth in SEQ ID NO: 3.

[0065] The modified silk fibroin of (1-i) can be composed of the amino acid sequence shown in SEQ ID NO:4.

[0066] The domain sequence of the second modified silk fibroin has an amino acid sequence with a reduced content of glycine residues compared to naturally derived silk fibroin. The second modified silk fibroin may have an amino acid sequence corresponding to at least one or more glycine residues in REP being substituted with other amino acid residues compared to naturally derived silk fibroin.

[0067] The domain sequence of the second modified fibroin, compared to the fibroin of natural origin, may have an amino acid sequence corresponding to at least one glycine residue in at least one or more of the motif sequences selected from GGX and GPGXX (wherein G represents a glycine residue, P represents a proline residue, and X represents an amino acid residue other than glycine) in REP, in which one glycine residue in the motif sequence is replaced by another amino acid residue.

[0068] In the second modified fibroin, the ratio of the motif sequence in which the glycine residue is substituted with another amino acid residue may be 10% or more relative to the entire motif sequence.

[0069] The second modified silk fibroin comprises formula 1: [(A) n motif-REP] m The domain sequence shown in FIG. 1 and may have an amino acid sequence obtained by removing the amino acid residue (A) located closest to the C-terminus from the domain sequence. n The total number of amino acid residues of the amino acid sequence consisting of XGX (wherein X represents an amino acid residue other than glycine) contained in all REPs in the sequence obtained after the sequence from the motif to the C-terminus of the above-mentioned domain sequence is set to z, and the residues (A) located most on the C-terminal side are removed from the above-mentioned domain sequence. n When the total number of amino acid residues in the sequence from the motif to the C-terminus of the above-mentioned domain sequence is w, z / w is 30% or more, 40% or more, 50% or more, or 50.9% or more. (A) n The number of alanine residues in the motif may be 83% or more, preferably 86% or more, more preferably 90% or more, further preferably 95% or more, and even more preferably 100% (meaning composed only of alanine residues) relative to the total number of amino acid residues.

[0070] The second modified silk fibroin preferably increases the proportion of amino acid sequences consisting of XGX by replacing one glycine residue in the GGX motif with another amino acid residue. In the second modified silk fibroin, the proportion of amino acid sequences consisting of GGX in the domain sequence is preferably 30% or less, more preferably 20% or less, further preferably 10% or less, further preferably 6% or less, further preferably 4% or less, and particularly preferably 2% or less. The proportion of amino acid sequences consisting of GGX in the domain sequence can be calculated by the same method as the calculation method for the proportion of amino acid sequences consisting of XGX (z / w) described below.

[0071] The calculation method of z / w is further described in detail. First, in the formula 1: [(A) n motif-REP] m In the silk fibroin (modified silk fibroin or naturally derived silk fibroin) having the domain sequence shown, the C-terminal end of (A) is removed from the domain sequence. n From all REPs contained in the sequence obtained after the motif to the C-terminus of the domain sequence, extract the amino acid sequence consisting of XGX. The total number of amino acid residues constituting XGX is z. For example, when 50 amino acid sequences consisting of XGX are extracted (no repetitions), z is 50×3=150. In addition, if there is an X contained in two XGXs (intermediate X), for example, an amino acid sequence consisting of XGXGX, the repetitive portion will be deducted from the calculation (in the case of XGXGX, there are 5 amino acid residues). w is the residue (A) located closest to the C-terminus removed from the domain sequence. n The total number of amino acid residues contained in the sequence from the motif to the C-terminus of the domain sequence. Figure 1 In the case of the domain sequence shown, w is 4+50+4+100+4+10+4+20+4+30=230 (the C-terminal end (A) has been removed). n Then, z / w (%) can be calculated by dividing z by w.

[0072] Here, the z / w of naturally derived silk fibroin is described. First, as described above, the silk fibroin with amino acid sequence information registered in NCBI GenBank was confirmed by the method mentioned above, and 663 types of silk fibroin were extracted (of which 415 types were derived from spiders). According to the formula 1 included in all the extracted silk fibroin: [(A) n motif-REP] mThe amino acid sequence of naturally derived silk fibroin containing the domain sequence shown above and containing an amino acid sequence consisting of GGX at a ratio of 6% or less was calculated using the above-described method. The z / w ratio of naturally derived silk fibroin was found to be less than 50.9% (with a maximum of 50.86%).

[0073] In the second modified fibroin, z / w is preferably 50.9% or more, more preferably 56.1% or more, further preferably 58.7% or more, further preferably 70% or more, and further preferably 80% or more. The upper limit of z / w is not particularly limited and can be, for example, 95% or less.

[0074] For example, the second modified silk fibroin can be obtained by performing the modification in the following manner, namely, replacing at least a portion of the base sequence encoding the glycine residue from the gene sequence of the cloned natural silk fibroin, and making it encode other amino acid residues. At this time, as the modified glycine residue, a glycine residue in the GGX motif and the GPGXX motif can be selected, or the replacement can be performed by setting the z / w to 50.9% or more. In addition, for example, an amino acid sequence that meets the above-mentioned embodiment can be designed based on the amino acid sequence of the natural silk fibroin, and obtained by chemically synthesizing a nucleic acid encoding the designed amino acid sequence. In any case, in addition to the modification equivalent to replacing the glycine residue in REP with other amino acid residues in the amino acid sequence of the natural silk fibroin, further amino acid sequence modification equivalent to replacement, deletion, insertion and / or addition of one or more amino acid residues can be performed.

[0075] The other amino acid residues are not particularly limited as long as they are amino acid residues other than glycine residues, but are preferably hydrophobic amino acid residues such as valine (V) residues, leucine (L) residues, isoleucine (I) residues, methionine (M) residues, proline (P) residues, phenylalanine (F) residues, and tryptophan (W) residues, and hydrophilic amino acid residues such as glutamine (Q) residues, asparagine (N) residues, serine (S) residues, lysine (K) residues, and glutamic acid (E) residues. More preferred are valine (V) residues, leucine (L) residues, isoleucine (I) residues, phenylalanine (F) residues, and glutamine (Q) residues, and even more preferred is glutamine (Q) residue.

[0076] As a more specific example of the second modified silk fibroin, there can be listed a modified silk fibroin comprising an amino acid sequence having a sequence identity of 90% or more with the amino acid sequence shown in (2-i) sequence number 6 (Met-PRT380), sequence number 7 (Met-PRT410), sequence number 8 (Met-PRT525) or sequence number 9 (Met-PRT799), or (2-ii) sequence number 6, sequence number 7, sequence number 8 or sequence number 9.

[0077] The modified silk fibroin of (2-i) is described. The amino acid sequence shown in sequence number 6 is an amino acid sequence obtained by replacing all the GGX in REP of the amino acid sequence shown in sequence number 10 (Met-PRT313) corresponding to the naturally derived silk fibroin with GQX. The amino acid sequence shown in sequence number 7 is obtained by replacing (A) from the N-terminal side to the C-terminal side in the amino acid sequence shown in sequence number 6. n The motif was deleted every 2 and a [(A) n Motif-REP]. The amino acid sequence shown in SEQ ID NO: 8 is in each (A) of the amino acid sequence shown in SEQ ID NO: 7. n Two alanine residues were inserted into the C-terminal side of the motif, and some glutamine (Q) residues were further replaced with serine (S) residues, and some amino acids on the C-terminal side were deleted so that the molecular weight was almost the same as that of SEQ ID NO: 7. The amino acid sequence set forth in SEQ ID NO: 9 is a sequence obtained by repeating four times a region of the 20 domain sequences present in the amino acid sequence set forth in SEQ ID NO: 7 (in which several amino acid residues on the C-terminal side of the region are replaced), with the specified hinge sequence and His tag sequence added to the C-terminus of the sequence.

[0078] The z / w value of the amino acid sequence set forth in SEQ ID NO: 10 (equivalent to naturally derived silk fibroin) is 46.8%. The z / w values ​​for the amino acid sequences set forth in SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9 are 58.7%, 70.1%, 66.1%, and 70.0%, respectively. Furthermore, the x / y values ​​for the amino acid sequences set forth in SEQ ID NO: 10, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, with a sawtooth ratio (described below) of 1:1.8 to 11.3, are 15.0%, 15.0%, 93.4%, 92.7%, and 89.8%, respectively.

[0079] The modified silk fibroin of (2-i) can be composed of the amino acid sequence shown in SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 or SEQ ID NO: 9.

[0080] The modified silk fibroin of (2-ii) comprises an amino acid sequence having a sequence identity of 90% or more to the amino acid sequence of SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 or SEQ ID NO: 9. The modified silk fibroin of (2-ii) also comprises formula 1: [(A) n motif-REP] m The sequence identity is preferably 95% or greater.

[0081] The modified silk fibroin of (2-ii) has a sequence identity of more than 90% with the amino acid sequence shown in SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 or SEQ ID NO: 9, and when the total number of amino acid residues of the amino acid sequence composed of XGX (wherein X represents an amino acid residue other than glycine) contained in REP is set to z and the total number of amino acid residues of REP in the above-mentioned domain sequence is set to w, z / w is preferably 50.9% or more.

[0082] The second modified silk fibroin may include a tag sequence at either or both of the N-terminus and the C-terminus, thereby enabling separation, immobilization, detection, and visualization of the modified silk fibroin.

[0083] As a tag sequence, for example, an affinity tag that utilizes specific affinity (binding property, affinity) with other molecules can be listed. As a specific example of an affinity tag, a histidine tag (His tag) can be listed. The His tag is a short peptide composed of about 4 to 10 histidine residues arranged in an array, and has the property of specifically binding to metal ions such as nickel, and can therefore be used for the separation of modified silk core protein by chelating metal chromatography. As a specific example of a tag sequence, for example, the amino acid sequence shown in sequence number 11 (an amino acid sequence comprising a His tag sequence and a hinge sequence) can be listed.

[0084] Alternatively, tag sequences such as glutathione-S-transferase (GST) that specifically binds to glutathione and maltose binding protein (MBP) that specifically binds to maltose can be used.

[0085] Furthermore, "epitope tags" that utilize antigen-antibody reactions can also be used. By adding a peptide (epitope) that displays antigenicity as a tag sequence, antibodies against the epitope can be bound. Examples of epitope tags include HA (peptide sequence of influenza virus hemagglutinin) tags, myc tags, and FLAG tags. By utilizing epitope tags, modified silk fibroin can be easily purified with high specificity.

[0086] Furthermore, a tag obtained by removing the tag sequence using a specific protease can also be used. Alternatively, the modified silk fibroin after the tag sequence is removed can be recovered by treating the protein adsorbed via the tag sequence with a protease.

[0087] As more specific examples of modified silk fibroin containing a tag sequence, there can be listed modified silk fibroin comprising an amino acid sequence having a sequence identity of more than 90% with the amino acid sequence shown in (2-iii) sequence number 12 (PRT380), sequence number 13 (PRT410), sequence number 14 (PRT525) or sequence number 15 (PRT799), or the amino acid sequence shown in (2-iv) sequence number 12, sequence number 13, sequence number 14 or sequence number 15.

[0088] The amino acid sequences shown in SEQ ID NO: 16 (PRT313), SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15 are obtained by adding the amino acid sequence shown in SEQ ID NO: 11 (including a His tag sequence and a hinge sequence) to the N-termini of the amino acid sequences shown in SEQ ID NO: 10, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, respectively.

[0089] The modified silk fibroin of (2-iii) can be composed of the amino acid sequence shown in SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14 or SEQ ID NO: 15.

[0090] The modified silk fibroin of (2-iv) comprises an amino acid sequence having a sequence identity of 90% or more to the amino acid sequence of SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14 or SEQ ID NO: 15. The modified silk fibroin of (2-iv) also comprises Formula 1: [(A) n motif-REP] m The sequence identity is preferably 95% or greater.

[0091] The modified silk fibroin of (2-iv) has a sequence identity of more than 90% with the amino acid sequence shown in SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14 or SEQ ID NO: 15, and when the total number of amino acid residues of the amino acid sequence composed of XGX (wherein X represents an amino acid residue other than glycine) contained in REP is set to z and the total number of amino acid residues of REP in the above-mentioned domain sequence is set to w, z / w is preferably greater than 50.9%.

[0092] The second modified silk fibroin may contain a secretion signal for releasing the protein produced in the recombinant protein production system to the outside of the host. The sequence of the secretion signal can be appropriately set according to the host species.

[0093] The domain sequence of the third modified silk fibroin has (A) compared with the natural silk fibroin.n The amino acid sequence of the modified silk fibroin domain sequence may have a deletion equivalent to at least one or more (A) compared to the natural silk fibroin. n The amino acid sequence of the motif.

[0094] The third modified silk fibroin may have a 10-40% (A) missing portion of the silk fibroin from natural sources. n The amino acid sequence of the motif.

[0095] The third domain sequence of the modified silk fibroin may have a domain sequence equivalent to at least 1 to 3 (A) from the N-terminal side to the C-terminal side compared to the natural silk fibroin. n One missing (A) in the motif n The amino acid sequence of the motif.

[0096] The third domain sequence of the modified silk fibroin may have a structure equivalent to at least two consecutive (A) sequences repeated sequentially from the N-terminal side to the C-terminal side, compared to the naturally derived silk fibroin. n Motif deletion and one (A) n Amino acid sequence of the motif deletion.

[0097] The third modified silk fibroin domain sequence may have a sequence corresponding to at least one occurrence every two from the N-terminal side to the C-terminal side (A) n Amino acid sequence of the motif deletion.

[0098] The third modified silk fibroin comprises formula 1: [(A) n motif-REP] m The domain sequence shown in FIG. 1 may have the following amino acid sequence: ie, two adjacent amino acids [(A) n The number of amino acid residues of the REP in the motif-REP] unit is set to 1, and the number of amino acid residues of the REP with the smaller number of amino acid residues is set to 1, and the ratio of the number of amino acid residues of the other REP is 1.8 to 11.3 for the two adjacent [(A) n The maximum value of the sum of the amino acid residue numbers of the motif-REP] units is x, and when the total number of amino acid residues in the domain sequence is y, x / y is 20% or more, 30% or more, 40% or more, or 50% or more. (A) n The number of alanine residues in the motif may be 83% or more, preferably 86% or more, more preferably 90% or more, further preferably 95% or more, and even more preferably 100% (meaning composed only of alanine residues) relative to the total number of amino acid residues.

[0099] Reference Figure 1 The calculation method of x / y is described in further detail. Figure 1 The domain sequence after removing the N-terminal sequence and the C-terminal sequence from the modified silk fibroin is shown. The domain sequence has (A) from the N-terminal side (left side) n Motif-1st REP (50 amino acid residues)-(A) n Motif-2 REP (100 amino acid residues)-(A) n Motif-3rd REP (10 amino acid residues)-(A) n Motif-4th REP (20 amino acid residues)-(A) n Motif-5th REP (30 amino acid residues)-(A) n The sequence of the motif.

[0100] Select two adjacent [(A) n Motif-REP] unit. In this case, there may also be unselected [(A) n motif-REP] unit. Figure 1 Mode 1 (comparison of the 1st REP and the 2nd REP, and comparison of the 3rd REP and the 4th REP), Mode 2 (comparison of the 1st REP and the 2nd REP, and comparison of the 4th REP and the 5th REP), Mode 3 (comparison of the 2nd REP and the 3rd REP, and comparison of the 4th REP and the 5th REP), and Mode 4 (comparison of the 1st REP and the 2nd REP) are shown. In addition, there are other selection methods.

[0101] Then, for each pattern, select two adjacent [(A) n The number of amino acid residues of each REP in the [motif-REP] unit is compared. The one with the fewer amino acid residues is set to 1, and the ratio of the number of amino acid residues of the other is calculated, and the comparison is made in this way. For example, when comparing the 1st REP (50 amino acid residues) with the 2nd REP (100 amino acid residues), the 1st REP with the fewer amino acid residues is set to 1, and the ratio of the number of amino acid residues of the 2nd REP is 100 / 50=2. Similarly, when comparing the 4th REP (20 amino acid residues) with the 5th REP (30 amino acid residues), the 4th REP with the fewer amino acid residues is set to 1, and the ratio of the number of amino acid residues of the 5th REP is 30 / 20=1.5.

[0102] Figure 1 In the figure, the solid line indicates the ratio of the number of amino acid residues of the other side to the number of amino acid residues of 1.8 to 11.3 when the side with the smaller number of amino acid residues is set to 1 [(A) nIn this specification, this ratio is referred to as the sawtooth ratio. The dotted line represents the ratio of the number of amino acid residues of the other side when the number of amino acid residues of the side with the smaller number is set to 1, which is less than 1.8 or greater than 11.3 [(A) n motif-REP] units.

[0103] In each mode, two adjacent ones [(A) n The sum of all amino acid residues in the motif-REP] unit (not only REP, but also (A) n The sum of the added values ​​is compared, and the sum of the patterns with the largest sum (the maximum sum) is set to x. Figure 1 In the example shown, the total value of mode 1 is the largest.

[0104] Then, x / y (%) can be calculated by dividing x by the total number of amino acid residues y in the domain sequence.

[0105] In the third modified silk fibroin, x / y is preferably 50% or more, more preferably 60% or more, further preferably 65% ​​or more, further preferably 70% or more, further preferably 75% or more, and particularly preferably 80% or more. The upper limit of x / y is not particularly limited, and for example, it can be 100% or less. When the sawtooth ratio is 1:1.9 to 11.3, x / y is preferably 89.6% or more, when the sawtooth ratio is 1:1.8 to 3.4, x / y is preferably 77.1% or more, when the sawtooth ratio is 1:1.9 to 8.4, x / y is preferably 75.9% or more, and when the sawtooth ratio is 1:1.9 to 4.1, x / y is preferably 64.2% or more.

[0106] The third modified silk fibroin has multiple domain sequences (A) n For modified silk fibroin in which at least seven of the motifs consist exclusively of alanine residues, the ratio x / y is preferably 46.4% or greater, more preferably 50% or greater, even more preferably 55% or greater, even more preferably 60% or greater, even more preferably 70% or greater, and particularly preferably 80% or greater. The upper limit of x / y is not particularly limited, but may be 100% or less.

[0107] Here, the x / y of natural silk fibroin is described. First, as described above, the silk fibroin with amino acid sequence information registered in NCBI GenBank was confirmed by the method mentioned above, and 663 types of silk fibroin were extracted (of which 415 types were from spiders). According to the formula 1: [(A)] n motif-REP] mThe amino acid sequence of naturally derived silk fibroin composed of the domain sequence shown above was used to calculate x / y, and the results showed that the x / y ratio of naturally derived silk fibroin was less than 64.2% (the maximum was 64.14%).

[0108] For example, the gene sequence encoding (A) can be modified so that x / y is 64.2% or more from the naturally-occurring silk fibroin gene sequence obtained by cloning. n Alternatively, for example, one or more of the amino acid sequences of the naturally derived silk fibroin may be deleted so that x / y is set to 64.2% or more. n The amino acid sequence in which the motif is deleted is obtained by chemically synthesizing a nucleic acid encoding the designed amino acid sequence. In any case, except for the deletion of the amino acid sequence equivalent to that of the natural source silk fibroin (A) n In addition to the modification of the motif, further amino acid sequence modification corresponding to substitution, deletion, insertion and / or addition of one or more amino acid residues can be performed.

[0109] As a more specific example of the third modified silk fibroin, there can be listed a modified silk fibroin comprising an amino acid sequence having a sequence identity of 90% or more with the amino acid sequence shown in (3-i) sequence number 17 (Met-PRT399), sequence number 7 (Met-PRT410), sequence number 8 (Met-PRT525) or sequence number 9 (Met-PRT799), or (3-ii) sequence number 17, sequence number 7, sequence number 8 or sequence number 9.

[0110] The modified silk fibroin of (3-i) is described. The amino acid sequence represented by SEQ ID NO: 17 corresponds to the amino acid sequence represented by SEQ ID NO: 10 (Met-PRT313) of naturally derived silk fibroin, wherein (A) n The motif was deleted every 2 and a [(A) n Motif-REP]. The amino acid sequence shown in SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 is as shown in the description of the second modified silk fibroin.

[0111] The amino acid sequence represented by SEQ ID NO: 10 (equivalent to naturally derived silk fibroin) has a sawtooth ratio of 1:1.8 to 11.3, with an x / y value of 15.0%. The amino acid sequences represented by SEQ ID NO: 17 and the amino acid sequence represented by SEQ ID NO: 7 both have x / y values ​​of 93.4%. The amino acid sequence represented by SEQ ID NO: 8 has an x / y value of 92.7%. The amino acid sequence represented by SEQ ID NO: 9 has an x / y value of 89.8%. The z / w values ​​for the amino acid sequences represented by SEQ ID NO: 10, SEQ ID NO: 17, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9 are 46.8%, 56.2%, 70.1%, 66.1%, and 70.0%, respectively.

[0112] The modified silk fibroin of (3-i) can be composed of the amino acid sequence shown in SEQ ID NO: 17, SEQ ID NO: 7, SEQ ID NO: 8 or SEQ ID NO: 9.

[0113] The modified silk fibroin of (3-ii) comprises an amino acid sequence having a sequence identity of 90% or more to the amino acid sequence of SEQ ID NO: 17, SEQ ID NO: 7, SEQ ID NO: 8 or SEQ ID NO: 9. The modified silk fibroin of (3-ii) also comprises formula 1: [(A) n motif-REP] m The sequence identity is preferably 95% or greater.

[0114] The modified silk fibroin of (3-ii) has a sequence identity of more than 90% with the amino acid sequence shown in SEQ ID NO: 17, SEQ ID NO: 7, SEQ ID NO: 8 or SEQ ID NO: 9, and the two adjacent [(A) n The number of amino acid residues of the REP in the motif-REP] unit is set to 1, and the ratio of the number of amino acid residues of the REP with the smaller number of amino acid residues is set to 1.8 to 11.3 (the sawtooth ratio is 1:1.8 to 11.3) for the adjacent two [(A) n When the maximum value of the total value of the amino acid residue numbers of the [motif-REP] units is x and the total number of amino acid residues in the domain sequence is y, x / y is preferably 64.2% or more.

[0115] The third modified silk fibroin may contain the tag sequence at either or both of the N-terminus and the C-terminus.

[0116] As more specific examples of modified silk fibroin containing a tag sequence, there can be listed modified silk fibroin comprising an amino acid sequence having a sequence identity of more than 90% with the amino acid sequence shown in (3-iii) sequence number 18 (PRT399), sequence number 13 (PRT410), sequence number 14 (PRT525) or sequence number 15 (PRT799), or the amino acid sequence shown in (3-iv) sequence number 18, sequence number 13, sequence number 14 or sequence number 15.

[0117] The amino acid sequences shown in SEQ ID NO: 18, SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 15 are obtained by adding the amino acid sequence shown in SEQ ID NO: 11 (including a His tag sequence and a hinge sequence) to the N-termini of the amino acid sequences shown in SEQ ID NO: 17, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, respectively.

[0118] The modified silk fibroin of (3-iii) can be composed of the amino acid sequence shown in SEQ ID NO: 18, SEQ ID NO: 13, SEQ ID NO: 14 or SEQ ID NO: 15.

[0119] The modified silk fibroin of (3-iv) comprises an amino acid sequence having a sequence identity of 90% or more to the amino acid sequence of SEQ ID NO: 18, SEQ ID NO: 13, SEQ ID NO: 14 or SEQ ID NO: 15. The modified silk fibroin of (3-iv) also comprises Formula 1: [(A) n motif-REP] m The sequence identity is preferably 95% or greater.

[0120] The modified silk fibroin of (3-iv) has a sequence identity of more than 90% with the amino acid sequence shown in SEQ ID NO: 18, SEQ ID NO: 13, SEQ ID NO: 14 or SEQ ID NO: 15, and the two adjacent [(A) n The number of amino acid residues of the REP in the motif-REP] unit is set to 1, and the number of amino acid residues of the REP with the smaller number of amino acid residues is set to 1, and the ratio of the number of amino acid residues of the other REP is 1.8 to 11.3 for the two adjacent [(A) n When the maximum value of the total value of the amino acid residue numbers of the [motif-REP] units is x and the total number of amino acid residues in the domain sequence is y, x / y is preferably 64.2% or more.

[0121] The third modified silk fibroin may contain a secretion signal for releasing the protein produced by the recombinant protein production system to the outside of the host. The sequence of the secretion signal can be appropriately set according to the host species.

[0122] The structural domain sequence of the fourth modified silk fibroin has (A) compared with the natural silk fibroin nThe amino acid sequence of the modified silk fibroin with reduced motif content and reduced glycine residue content. The structural domain sequence of the fourth modified silk fibroin may have at least one or more (A) equivalent to the natural silk fibroin. n The amino acid sequence is characterized by a motif deletion and substitution of one or more glycine residues in at least REP with other amino acid residues. In other words, the fourth modified silk fibroin is a modified silk fibroin that combines the characteristics of the second and third modified silk fibroin described above. Specific embodiments are as described for the second and third modified silk fibroin.

[0123] More specific examples of the fourth modified silk fibroin include modified silk fibroin comprising an amino acid sequence having 90% or greater sequence identity with the amino acid sequence set forth in (4-i) SEQ ID NO: 7 (Met-PRT410), SEQ ID NO: 8 (Met-PRT525), SEQ ID NO: 9 (Met-PRT799), SEQ ID NO: 13 (PRT410), SEQ ID NO: 14 (PRT525), or SEQ ID NO: 15 (PRT799), or (4-ii) the amino acid sequence set forth in SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 14, or SEQ ID NO: 15. Specific embodiments of the modified silk fibroin comprising the amino acid sequence set forth in SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 14, or SEQ ID NO: 15 are as described above.

[0124] The domain sequence of the 5th modified silk fibroin can have an amino acid sequence equivalent to one or more amino acid residues in REP being replaced with large hydrophobicity index amino acid residues and / or one or more large hydrophobicity index amino acid residues being inserted into REP, and comprising a local large hydrophobicity index region, compared with the silk fibroin from natural sources.

[0125] The local high hydrophobicity index region is preferably composed of 2 to 4 consecutive amino acid residues.

[0126] The amino acid residue that is an indicator of high hydrophobicity is more preferably an amino acid residue selected from isoleucine (I), valine (V), leucine (L), phenylalanine (F), cysteine ​​(C), methionine (M) and alanine (A).

[0127] The fifth modified silk fibroin can be modified to be equivalent to replacing one or more amino acid residues in REP with large hydrophobicity index amino acid residues and / or inserting one or more large hydrophobicity index amino acid residues into REP compared to silk fibroin from natural sources. In addition, it can also be modified to be equivalent to replacing, deleting, inserting and / or adding one or more amino acid residues compared to silk fibroin from natural sources.

[0128] For example, the fifth modified silk fibroin can be obtained by replacing one or more hydrophilic amino acid residues (e.g., amino acid residues with a negative hydrophobicity index) in REP with hydrophobic amino acid residues (e.g., amino acid residues with a positive hydrophobicity index) from the gene sequence of the cloned natural silk fibroin, and / or inserting one or more hydrophobic amino acid residues into REP. Furthermore, for example, an amino acid sequence equivalent to replacing one or more hydrophilic amino acid residues in REP with hydrophobic amino acid residues and / or inserting one or more hydrophobic amino acid residues into REP from the amino acid sequence of the natural silk fibroin can be designed and obtained by chemically synthesizing a nucleic acid encoding the designed amino acid sequence. In any case, in addition to modifications equivalent to replacing one or more hydrophilic amino acid residues in REP with hydrophobic amino acid residues and / or inserting one or more hydrophobic amino acid residues into REP from the amino acid sequence of the natural silk fibroin, further amino acid sequence modifications equivalent to substitution, deletion, insertion, and / or addition of one or more amino acid residues can be performed.

[0129] The fifth modified silk fibroin comprises formula 1: [(A) n motif-REP] m The domain sequence shown in FIG. 1 and the amino acid sequence may be as follows: (A) located at the most C-terminal side is removed from the above domain sequence. n The total number of amino acid residues contained in the region where the average value of the hydrophobicity index of four consecutive amino acid residues is 2.6 or more is defined as p, and the residues located closest to the C-terminus (A) are removed from the domain sequence. n When the total number of amino acid residues contained in the sequence obtained from the motif to the C-terminus of the above-mentioned domain sequence is q, p / q is 6.2% or more.

[0130] As an index of the hydrophobicity of amino acid residues, a known index was used (Hydropathy index: Kyte J, & Doolittle R (1982) "A simple method for displaying the hydropathic character of a protein", J. Mol. Biol., 157, pp. 105-132). Specifically, the hydrophobicity index (hydrophilic index, hereinafter also referred to as "HI") of each amino acid is shown in Table 1 below.

[0131] [Table 1]

[0132] amino acids HI amino acids HI Isoleucine (Ile) 4.5 Tryptophan (Trp) -0.9 Valine (Val) 4.2 Tyrosine (Tyr) -1.3 Leucine (Leu) 3.8 Proline (Pro) -1.6 Phenylalanine (Phe) 2.8 Histidine (His) -3.2 Cysteine ​​(Cys) 2.5 Asparagine (Asn) -3.5 Methionine (Met) 1.9 Aspartic acid (Asp) -3.5 Alanine (Ala) 1.8 Glutamine (Gln) -3.5 Glycine (Gly) -0.4 Glutamate (Glu) -3.5 Threonine (Thr) -0.7 Lysine (Lys) -3.9 Serine (Ser) -0.8 Arginine (Arg) -4.5

[0133] The calculation method of p / q is further explained in detail. In the calculation, the formula 1 is used: [(A) n motif-REP] m The domain sequence shown is excluding the domain located closest to the C-terminus (A). n The sequence obtained from the sequence from the motif to the C-terminus of the domain sequence (hereinafter referred to as "sequence A"). First, among all REPs contained in sequence A, the average value of the hydrophobicity index of 4 consecutive amino acid residues is calculated. The average value of the hydrophobicity index is obtained by dividing the sum of the HI of each amino acid residue contained in the 4 consecutive amino acid residues by 4 (the number of amino acid residues). The average value of the hydrophobicity index is obtained for all 4 consecutive amino acid residues (each amino acid residue is used for the calculation of 1 to 4 average values). Next, the region where the average value of the hydrophobicity index of 4 consecutive amino acid residues is 2.6 or above is determined. Even if a certain amino acid residue belongs to multiple "4 consecutive amino acid residues with an average value of the hydrophobicity index of 2.6 or above", it will be included in the region as one amino acid residue. Moreover, the total number of amino acid residues contained in the region is p. In addition, the total number of amino acid residues contained in sequence A is q.

[0134] For example, when 20 "4 consecutive amino acid residues with an average hydrophobicity index of 2.6 or more" are extracted (without duplication), the region with an average hydrophobicity index of 4 consecutive amino acid residues of 2.6 or more contains 20 consecutive 4 amino acid residues (without duplication), and p is 20×4=80. In addition, for example, when only one amino acid residue is repeated in 2 "4 consecutive amino acid residues with an average hydrophobicity index of 2.6 or more", the region with an average hydrophobicity index of 4 consecutive amino acid residues of 2.6 or more contains 7 amino acid residues (p=2×4-1=7, "-1" means deducting the repeated part). For example, Figure 2 In the domain sequence shown, there are 7 "4 consecutive amino acid residues with an average hydrophobicity index of 2.6 or more" without duplication, so p is 7×4=28. In addition, for example, Figure 2 In the domain sequence shown, q is 4+50+4+40+4+10+4+20+4+30=170 (excluding the last (A) at the C-terminal side). n Then, by dividing p by q, p / q (%) can be calculated. Figure 2 28 / 170=16.47%.

[0135] In the fifth modified silk fibroin, p / q is preferably 6.2% or more, more preferably 7% or more, further preferably 10% or more, further preferably 20% or more, and further preferably 30% or more. The upper limit of p / q is not particularly limited and can be, for example, 45% or less.

[0136] For example, for the amino acid sequence of the cloned natural source silk fibroin, by replacing one or more hydrophilic amino acid residues (e.g., amino acid residues with a negative hydrophobic index) in REP with hydrophobic amino acid residues (e.g., amino acid residues with a positive hydrophobic index), and / or inserting one or more hydrophobic amino acid residues into REP so that it satisfies the above-mentioned p / q condition, it is transformed into an amino acid sequence containing a local large hydrophobic index region, thereby obtaining the fifth modified silk fibroin. In addition, for example, an amino acid sequence that satisfies the above-mentioned p / q condition can also be designed based on the amino acid sequence of the natural source silk fibroin, and obtained by chemically synthesizing a nucleic acid encoding the designed amino acid sequence. In any case, compared to the natural source silk fibroin, in addition to the modification equivalent to replacing one or more amino acid residues in REP with amino acid residues with a large hydrophobic index and / or inserting one or more amino acid residues with a large hydrophobic index into REP, a modification equivalent to substitution, deletion, insertion and / or addition of one or more amino acid residues can also be performed.

[0137] There are no particular restrictions on the amino acid residues that are indicators of high hydrophobicity, but preferred are isoleucine (I), valine (V), leucine (L), phenylalanine (F), cysteine ​​(C), methionine (M) and alanine (A), and more preferred are valine (V), leucine (L) and isoleucine (I).

[0138] As a more specific example of the fifth modified silk fibroin, there can be listed modified silk fibroin comprising an amino acid sequence having a sequence identity of more than 90% with the amino acid sequence shown in (5-i) sequence number 19 (Met-PRT720), sequence number 20 (Met-PRT665) or sequence number 21 (Met-PRT666), or the amino acid sequence shown in (5-ii) sequence number 19, sequence number 20 or sequence number 21.

[0139] The modified silk fibroin of (5-i) is described. The amino acid sequence shown in sequence number 19 is compared with the amino acid sequence shown in sequence number 7 (Met-PRT410), except for the terminal domain sequence on the C-terminal side, an amino acid sequence (VLI) consisting of three amino acid residues is inserted at two locations every other REP, and then a part of the glutamine (Q) residues is replaced with a serine (S) residue, and a part of the amino acids on the C-terminal side is deleted. The amino acid sequence shown in sequence number 20 is compared with the amino acid sequence shown in sequence number 8 (Met-PRT525), and an amino acid sequence (VLI) consisting of three amino acid residues is inserted at one location every other REP. The amino acid sequence shown in sequence number 21 is compared with the amino acid sequence shown in sequence number 8, and an amino acid sequence (VLI) consisting of three amino acid residues is inserted at two locations every other REP.

[0140] The modified silk fibroin of (5-i) can be composed of the amino acid sequence shown in SEQ ID NO: 19, SEQ ID NO: 20, or SEQ ID NO: 21.

[0141] The modified silk fibroin of (5-ii) comprises an amino acid sequence having a sequence identity of 90% or more to the amino acid sequence of SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. The modified silk fibroin of (5-ii) also comprises formula 1: [(A) n motif-REP] m The sequence identity is preferably 95% or greater.

[0142] The modified silk fibroin of (5-ii) has a sequence identity of 90% or more with the amino acid sequence of SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21, and wherein (A) located at the most C-terminal side is removed from the domain sequence. n Of all REPs contained in the sequence obtained by deriving the sequence from the motif to the C-terminus of the domain sequence, the total number of amino acid residues contained in the region where the average value of the hydrophobicity index of four consecutive amino acid residues is 2.6 or more is defined as p, and the residues located closest to the C-terminus (A) are removed from the domain sequence. n When the total number of amino acid residues contained in the sequence from the motif to the C-terminus of the domain sequence is q, p / q is preferably 6.2% or more.

[0143] The fifth modified silk fibroin may comprise a tag sequence at either or both of the N-terminus and the C-terminus.

[0144] As more specific examples of modified silk fibroin containing a tag sequence, there can be listed modified silk fibroin containing an amino acid sequence having a sequence identity of more than 90% with the amino acid sequence shown in (5-iii) sequence number 22 (PRT720), sequence number 23 (PRT665) or sequence number 24 (PRT666), or the amino acid sequence shown in (5-iv) sequence number 22, sequence number 23 or sequence number 24.

[0145] The amino acid sequences represented by SEQ ID NOs: 22, 23, and 24 are obtained by adding the amino acid sequence represented by SEQ ID NOs: 11 (including a His tag sequence and a hinge sequence) to the N-termini of the amino acid sequences represented by SEQ ID NOs: 19, 20, and 21, respectively.

[0146] The modified silk fibroin of (5-iii) can be composed of the amino acid sequence shown in SEQ ID NO: 22, SEQ ID NO: 23 or SEQ ID NO: 24.

[0147] The modified silk fibroin of (5-iv) comprises an amino acid sequence having a sequence identity of 90% or more to the amino acid sequence shown in SEQ ID NO: 22, SEQ ID NO: 23 or SEQ ID NO: 24. The modified silk fibroin of (5-iv) also comprises Formula 1: [(A) n motif-REP] m The sequence identity is preferably 95% or greater.

[0148] The modified silk fibroin (5-iv) has a sequence identity of 90% or more with the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 23 or SEQ ID NO: 24, and wherein the amino acid sequence of (A) located at the most C-terminal side is removed from the domain sequence. n Of all REPs contained in the sequence obtained by deriving the sequence from the motif to the C-terminus of the domain sequence, the total number of amino acid residues contained in the region where the average value of the hydrophobicity index of four consecutive amino acid residues is 2.6 or more is defined as p, and the residues located closest to the C-terminus (A) are removed from the domain sequence. n When the total number of amino acid residues contained in the sequence from the motif to the C-terminus of the domain sequence is q, p / q is preferably 6.2% or more.

[0149] The fifth modified silk fibroin may contain a secretion signal for releasing the protein produced by the recombinant protein production system to the outside of the host. The sequence of the secretion signal can be appropriately set according to the host species.

[0150] The sixth modified silk fibroin has an amino acid sequence with a reduced glutamine residue content compared to silk fibroin from natural sources.

[0151] The sixth modified fibroin preferably contains at least one motif selected from the group consisting of a GGX motif and a GPGXX motif in the amino acid sequence of REP.

[0152] When the sixth modified fibroin contains a GPGXX motif in REP, the GPGXX motif content is usually 1% or more, may be 5% or more, and preferably 10% or more. The upper limit of the GPGXX motif content is not particularly limited and may be 50% or less or 30% or less.

[0153] In this specification, the "GPGXX motif content rate" is a value calculated by the following method.

[0154] In the formula 1: [(A) n motif-REP] m Or formula 2: [(A) n motif-REP] m -(A) n In the silk fibroin (modified silk fibroin or naturally derived silk fibroin) having the domain sequence shown in the motif, the C-terminal end of the (A) is removed from the domain sequence. n Of all REPs contained in the sequence obtained by multiplying the total number of GPGXX motifs contained in the region by 3 (i.e., equivalent to the total number of G and P in the GPGXX motif), the number is set as s, and the (A) located closest to the C-terminal side is removed from the domain sequence. n The sequence from the motif to the C-terminus of the domain sequence is removed (A) n When the total number of amino acid residues of all REPs obtained after the motif is set as t, the GPGXX motif content rate is calculated as s / t.

[0155] In the calculation of the GPGXX motif content, the motif (A) located closest to the C-terminus was removed from the domain sequence. n The purpose of selecting the sequence from the motif to the C-terminus of the domain sequence is to exclude the following influence: "(A) located at the most C-terminal side" n The sequence from the motif to the C-terminus of the domain sequence (equivalent to the sequence of REP) sometimes contains sequences with low correlation with the characteristic sequence of fibroin. When m is small (i.e., when the domain sequence is short), the calculation results of the GPGXX motif content will be affected. In addition, when the "GPGXX motif" is located at the C-terminus of REP, even if "XX" is "AA", for example, it is treated as a "GPGXX motif".

[0156] Figure 3 Schematic diagram showing the domain sequence of modified silk fibroin. Figure 3Let's explain in detail how to calculate the GPGXX motif content. Figure 3 The domain sequence of the modified silk fibroin shown ("[(A) n motif-REP] m -(A) n motif" type), all REPs are included in the "removal from the domain sequence from the (A) located at the most C-terminal side" n The sequence obtained from the sequence from the motif to the C-terminus of the domain sequence" ( Figure 3 Therefore, the number of GPGXX motifs used to calculate s is 7, and s is 7×3=21. Similarly, all REPs are included in the "region A" located at the most C-terminal side of the domain sequence. n The sequence obtained from the sequence from the motif to the C-terminus of the domain sequence" ( Figure 3 Therefore, (A) is further removed from the sequence. n The total number of amino acid residues of all REPs obtained after the motif is 50+40+10+20+30=150. Then, by dividing s by t, s / t (%) can be calculated. Figure 3 In the case of the modified silk fibroin, it is 21 / 150=14.0%.

[0157] The glutamine residue content in the sixth modified fibroin is preferably 9% or less, more preferably 7% or less, further preferably 4% or less, and particularly preferably 0%.

[0158] In this specification, the "glutamine residue content" is a value calculated by the following method.

[0159] In the formula 1: [(A) n motif-REP] m Or formula 2: [(A) n motif-REP] m -(A) n In the silk fibroin (modified silk fibroin or naturally derived silk fibroin) having the domain sequence shown in the motif, the C-terminal end of the (A) is removed from the domain sequence. n The sequence obtained by the sequence from the motif to the C-terminus of the domain sequence (equivalent to Figure 3 Of all REPs contained in the "region A" of the domain (the sequence of the region A), the total number of glutamine residues contained in the region is set to u, and the residues located closest to the C-terminus (A) are removed from the domain sequence. n The sequence from the motif to the C-terminus of the domain sequence is further removed (A) nWhen the total number of amino acid residues of all REPs obtained after the motif is set as t, the glutamine residue content is calculated as u / t. In the calculation of the glutamine residue content, the ratio is calculated as "removing the residues located at the most C-terminal side (A) from the domain sequence". n The reason for targeting the "sequence from the motif to the C-terminus of the domain sequence" is the same as the above reason.

[0160] The domain sequence of the sixth modified fibroin may have an amino acid sequence equivalent to one or more glutamine residues in REP being deleted or replaced with other amino acid residues, compared to the fibroin from natural sources.

[0161] The "other amino acid residues" may be any amino acid residue other than a glutamine residue, and are preferably amino acid residues having a hydrophobicity index greater than that of the glutamine residue. The hydrophobicity indexes of the amino acid residues are shown in Table 1.

[0162] As shown in Table 1, examples of amino acid residues having a hydrophobicity index greater than that of glutamine residues include amino acid residues selected from isoleucine (I), valine (V), leucine (L), phenylalanine (F), cysteine ​​(C), methionine (M), alanine (A), glycine (G), threonine (T), serine (S), tryptophan (W), tyrosine (Y), proline (P), and histidine (H). Among these, amino acid residues selected from isoleucine (I), valine (V), leucine (L), phenylalanine (F), cysteine ​​(C), methionine (M), and alanine (A) are more preferred, and amino acid residues selected from isoleucine (I), valine (V), leucine (L), and phenylalanine (F) are even more preferred.

[0163] The hydrophobicity of REP in the sixth modified fibroin is preferably -0.8 or greater, more preferably -0.7 or greater, further preferably 0 or greater, even more preferably 0.3 or greater, and particularly preferably 0.4 or greater. The upper limit of the hydrophobicity of REP is not particularly limited and may be 1.0 or less or 0.7 or less.

[0164] In this specification, the "hydrophobicity degree of REP" is a value calculated by the following method.

[0165] In the formula 1: [(A) n motif-REP] m Or formula 2: [(A) n motif-REP] m -(A) n In the silk fibroin (modified silk fibroin or naturally derived silk fibroin) having the domain sequence shown in the motif, the C-terminal end of the (A) is removed from the domain sequence. nThe sequence obtained by the sequence from the motif to the C-terminus of the domain sequence (equivalent to Figure 3 Of all REPs contained in the "region A" of the domain (the sequence of the region A), the sum of the hydrophobicity indices of the amino acid residues in the region is set to v, and the residues located closest to the C-terminus (A) are removed from the domain sequence. n The sequence from the motif to the C-terminus of the domain sequence is further removed (A) n When the total number of amino acid residues of all REPs obtained after the motif is set as t, the hydrophobicity of REP is calculated as v / t. In the calculation of the hydrophobicity of REP, the hydrophobicity of REP is calculated by "removing the residues (A) located at the most C-terminal side from the domain sequence". n The reason for targeting the "sequence from the motif to the C-terminus of the domain sequence" is the same as the above reason.

[0166] Compared with the silk fibroin of natural origin, the domain sequence of the sixth modified silk fibroin can undergo modifications equivalent to deleting one or more glutamine residues in REP and / or replacing one or more glutamine residues in REP with other amino acid residues, and can also undergo further amino acid sequence modifications equivalent to replacing, deleting, inserting and / or adding one or more amino acid residues.

[0167] For example, the sixth modified silk fibroin can be obtained by deleting one or more glutamine residues in REP and / or replacing one or more glutamine residues in REP with other amino acid residues from the gene sequence of the cloned naturally derived silk fibroin. Furthermore, for example, an amino acid sequence equivalent to deleting one or more glutamine residues in REP and / or replacing one or more glutamine residues in REP with other amino acid residues from the amino acid sequence of the naturally derived silk fibroin can be designed and obtained by chemically synthesizing a nucleic acid encoding the designed amino acid sequence.

[0168] As more specific examples of the sixth modified silk fibroin, there are listed the following: (6-i) sequence number 25 (Met-PRT888), sequence number 26 (Met-PRT965), sequence number 27 (Met-PRT889), sequence number 28 (Met-PRT916), sequence number 29 (Met-PRT918), sequence number 30 (Met-PRT699), sequence number 31 (Met-PRT698), sequence number 32 (Met -PRT966), a modified silk fibroin having an amino acid sequence shown in sequence number 41 (Met-PRT917) or sequence number 42 (Met-PRT1028), or a modified silk fibroin having an amino acid sequence having a sequence identity of more than 90% with the amino acid sequence shown in sequence number 25, sequence number 26, sequence number 27, sequence number 28, sequence number 29, sequence number 30, sequence number 31, sequence number 32, sequence number 41 or sequence number 42 (6-ii).

[0169] The modified silk fibroin of (6-i) is described. The amino acid sequence shown in sequence number 25 is an amino acid sequence obtained by replacing all QQ in the amino acid sequence (Met-PRT410) shown in sequence number 7 with VL. The amino acid sequence shown in sequence number 26 is an amino acid sequence obtained by replacing all QQ in the amino acid sequence shown in sequence number 7 with TS, and replacing the remaining Q with A. The amino acid sequence shown in sequence number 27 is an amino acid sequence obtained by replacing all QQ in the amino acid sequence shown in sequence number 7 with VL, and replacing the remaining Q with I. The amino acid sequence shown in sequence number 28 is an amino acid sequence obtained by replacing all QQ in the amino acid sequence shown in sequence number 7 with VI, and replacing the remaining Q with L. The amino acid sequence shown in sequence number 29 is an amino acid sequence obtained by replacing all QQ in the amino acid sequence shown in sequence number 7 with VF, and replacing the remaining Q with I.

[0170] The amino acid sequence set forth in SEQ ID NO: 30 is an amino acid sequence in which all QQ in the amino acid sequence set forth in SEQ ID NO: 8 (Met-PRT525) are substituted with VL. The amino acid sequence set forth in SEQ ID NO: 31 is an amino acid sequence in which all QQ in the amino acid sequence set forth in SEQ ID NO: 8 are substituted with VL, and the remaining Q is substituted with I.

[0171] The amino acid sequence shown in SEQ ID NO: 32 is an amino acid sequence obtained by repeating the region of the 20 domain sequences present in the amino acid sequence shown in SEQ ID NO: 7 (Met-PRT410) twice, replacing all QQ in the resulting sequence with VF, and replacing the remaining Q with I.

[0172] The amino acid sequence set forth in SEQ ID NO: 41 (Met-PRT917) is an amino acid sequence obtained by replacing all QQ in the amino acid sequence set forth in SEQ ID NO: 7 with LI, and replacing the remaining Q with V. The amino acid sequence set forth in SEQ ID NO: 42 (Met-PRT1028) is an amino acid sequence obtained by replacing all QQ in the amino acid sequence set forth in SEQ ID NO: 7 with IF, and replacing the remaining Q with T.

[0173] The glutamine residue content of the amino acid sequences represented by SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 41, and SEQ ID NO: 42 is 9% or less (Table 2).

[0174] [Table 2]

[0175] Modified silk fibroin Glutamine residue content GPGXX motif content The degree of hydrophobicity of REP Met-PRT410 (serial number 7) 17.7％ 27.9％ -1.52 Met-PRT888 (serial number 25) 6.3％ 27.9％ -0.07 Met-PRT965 (serial number 26) 0.0％ 27.9％ -0.65 Met-PRT889 (serial number 27) 0.0％ 27.9％ 0.35 Met-PRT916 (serial number 28) 0.0％ 27.9％ 0.47 Met-PRT918 (serial number 29) 0.0％ 27.9％ 0.45 Met-PRT699 (serial number 30) 3.6％ 26.4％ -0.78 Met-PRT698 (serial number 31) 0.0％ 26.4％ -0.03 Met-PRT966 (serial number 32) 0.0％ 28.0％ 0.35 Met-PRT917 (serial number 41) 0.0％ 27.9％ 0.46 Met-PRT1028 (serial number 42) 0.0％ 28.1％ 0.05

[0176] The modified silk fibroin of (6-i) can be composed of the amino acid sequence shown in sequence number 25, sequence number 26, sequence number 27, sequence number 28, sequence number 29, sequence number 30, sequence number 31, sequence number 32, sequence number 41 or sequence number 42.

[0177] The modified silk fibroin of (6-ii) comprises an amino acid sequence having a sequence identity of 90% or greater to the amino acid sequence of SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 41, or SEQ ID NO: 42. The modified silk fibroin of (6-ii) is also a protein comprising a domain sequence represented by Formula 1: [(A)n motif-REP]m or Formula 2: [(A)n motif-REP]m-(A)n motif. The sequence identity is preferably 95% or greater.

[0178] The modified silk fibroin of (6-ii) preferably has a glutamine residue content of 9% or less. Furthermore, the modified silk fibroin of (6-ii) preferably has a GPGXX motif content of 10% or more.

[0179] The sixth modified silk fibroin may include a tag sequence at either or both of the N-terminus and the C-terminus, thereby enabling separation, immobilization, detection, and visualization of the modified silk fibroin.

[0180] As more specific examples of modified silk fibroin containing a tag sequence, there can be listed modified silk fibroin comprising the amino acid sequence shown in (6-iii) sequence number 33 (PRT888), sequence number 34 (PRT965), sequence number 35 (PRT889), sequence number 36 (PRT916), sequence number 37 (PRT918), sequence number 38 (PRT699), sequence number 39 (PRT698), sequence number 40 (PRT966), sequence number 43 (PRT917) or sequence number 44 (PRT1028), or modified silk fibroin comprising an amino acid sequence having a sequence identity of more than 90% with the amino acid sequence shown in (6-iv) sequence number 33, sequence number 34, sequence number 35, sequence number 36, sequence number 37, sequence number 38, sequence number 39, sequence number 40, sequence number 43 or sequence number 44.

[0181] The amino acid sequences set forth in SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 43, and SEQ ID NO: 44 have the amino acid sequence set forth in SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 41, and SEQ ID NO: 42, respectively, with the amino acid sequence set forth in SEQ ID NO: 11 (including a His-tag sequence and a hinge sequence) added to the N-terminus. Since only the tag sequence was added to the N-terminus, the glutamine residue content did not change, and the glutamine residue content of the amino acid sequences set forth in SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 43, and SEQ ID NO: 44 was 9% or less (Table 3).

[0182] [Table 3]

[0183] Modified silk fibroin Glutamine residue content GPGXX motif content Degree of hydrophobicity of REP PRT888 (serial number 33) 6.3％ 27.9 -0.07 PRT965 (serial number 34) 0.0％ 27.9 -0.65 PRT889 (serial number 35) 0.0％ 27.9 0.35 PRT916 (serial number 36) 0.0％ 27.9 0.47 PRT918 (serial number 37) 0.0％ 27.9 0.45 PRT699 (serial number 38) 3.6％ 26.4 -0.78 PRT698 (serial number 39) 0.0％ 26.4 -0.03 PRT966 (serial number 40) 0.0％ 28.0 0.35 PRT917 (serial number 43) 0.0％ 27.9 0.46 PRT1028 (serial number 44) 0.0％ 28.1 0.05

[0184] The modified silk fibroin of (6-iii) can be composed of the amino acid sequence shown in sequence number 33, sequence number 34, sequence number 35, sequence number 36, sequence number 37, sequence number 38, sequence number 39, sequence number 40, sequence number 43 or sequence number 44.

[0185] The modified silk fibroin of (6-iv) comprises an amino acid sequence having a sequence identity of 90% or more to the amino acid sequence of SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 43, or SEQ ID NO: 44. The modified silk fibroin of (6-iv) also comprises Formula 1: [(A) n motif-REP] m Or formula 2: [(A) nmotif-REP] m -(A) n The protein has a domain sequence represented by the motif. The sequence identity is preferably 95% or more.

[0186] The modified silk fibroin of (6-iv) preferably has a glutamine residue content of 9% or less. Furthermore, the modified silk fibroin of (6-iv) preferably has a GPGXX motif content of 10% or more.

[0187] The sixth modified silk fibroin may contain a secretion signal for releasing the protein produced by the recombinant protein production system to the outside of the host. The sequence of the secretion signal can be appropriately set according to the host species.

[0188] The modified silk fibroin may be a modified silk fibroin having at least two or more characteristics among the characteristics of the first modified silk fibroin, the second modified silk fibroin, the third modified silk fibroin, the fourth modified silk fibroin, the fifth modified silk fibroin, and the sixth modified silk fibroin.

[0189] Modified silk fibroin can be either hydrophilic or hydrophobic. The sum of the hydrophobicity index (HI) of all amino acid residues constituting the modified silk fibroin is calculated, and then this sum is divided by the total number of amino acid residues to obtain a value (average HI). Hydrophobic modified silk fibroin refers to modified silk fibroin with this value (average HI) of 0 or greater. The hydrophobicity index is shown in Table 1. Furthermore, hydrophilic modified silk fibroin refers to modified silk fibroin with the aforementioned average HI less than 0.

[0190] Examples of hydrophobic modified silk fibroin include the sixth modified silk fibroin described above. More specific examples of hydrophobic modified silk fibroin include modified silk fibroin comprising the amino acid sequence set forth in SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, or SEQ ID NO: 43, and the amino acid sequence set forth in SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, or SEQ ID NO: 44.

[0191] Examples of hydrophilic modified silk fibroin include the first modified silk fibroin, the second modified silk fibroin, the third modified silk fibroin, the fourth modified silk fibroin, and the fifth modified silk fibroin. More specific examples of hydrophilic modified silk fibroin include modified silk fibroin comprising the amino acid sequence set forth in SEQ ID NO: 4, the amino acid sequence set forth in SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9, the amino acid sequence set forth in SEQ ID NO: 13, SEQ ID NO: 11, SEQ ID NO: 14, or SEQ ID NO: 15, the amino acid sequence set forth in SEQ ID NO: 18, the amino acid sequence set forth in SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9, the amino acid sequence set forth in SEQ ID NO: 17, SEQ ID NO: 11, SEQ ID NO: 14, or SEQ ID NO: 15, or the amino acid sequence set forth in SEQ ID NO: 19, SEQ ID NO: 20, or SEQ ID NO: 21.

[0192] (Protein Preparation Method)

[0193] For example, a host is transformed with an expression vector having a nucleic acid sequence encoding a protein and one or more regulatory sequences operably linked to the nucleic acid sequence, and the nucleic acid is expressed by the host, thereby producing the protein.

[0194] The preparation method of the gene encoding the protein is not particularly limited. For example, a gene encoding a natural structural protein can be used, and amplified and cloned using polymerase chain reaction (PCR) or the like, and the gene is prepared by this method or a chemical synthesis method. The chemical synthesis method of the gene is also not particularly limited. For example, the amino acid sequence information of the structural protein obtained from the NCBI network database, etc., and oligonucleotides can be automatically synthesized using AKTA oligopilot plus 10 / 100 (GE Healthcare Japan Co., Ltd.), and the oligonucleotides are connected using PCR or the like, and the gene is chemically synthesized by this method. At this time, in order to facilitate the purification and confirmation of the protein, the gene encoding the following protein can be synthesized: the protein is composed of the amino acid sequence obtained after adding the amino acid sequence consisting of the start codon and the His10 tag to the N-terminus of the above-mentioned amino acid sequence.

[0195] Regulatory sequences are sequences that control protein expression in the host (e.g., promoters, enhancers, ribosome binding sequences, transcription termination sequences, etc.), and can be appropriately selected based on the host species. As promoters, inducible promoters that function in host cells and can express induced proteins can also be used. Inducible promoters are promoters that can control transcription by physical factors such as the presence of an inducing substance (expression inducer), the absence of a repressor molecule, or the rise or fall of temperature, osmotic pressure, or pH.

[0196] The type of expression vector can be appropriately selected according to the host species, such as a plasmid vector, a viral vector, a cosmid vector, a fosmid vector, an artificial chromosome vector, etc. As the expression vector, it is preferred to use a vector that can autonomously replicate in the host cell or can be integrated into the host chromosome and contains a promoter at a position capable of transcribing the nucleic acid encoding the protein.

[0197] As the host, any of prokaryotes and eukaryotes such as yeast, filamentous fungi, insect cells, animal cells, and plant cells can be preferably used.

[0198] Preferred examples of prokaryotes include bacteria belonging to the genera Escherichia, Brevibacillus, Serratia, Bacillus, Microbacterium, Brevibacterium, Corynebacterium, and Pseudomonas. Examples of microorganisms belonging to the genus Escherichia include Escherichia coli. Examples of microorganisms belonging to the genus Brevibacillus include Brevibacillus terrestris. Examples of microorganisms belonging to the genus Serratia include Serratia liquefaciens. Examples of microorganisms belonging to the genus Bacillus include Bacillus subtilis. Examples of microorganisms belonging to the genus Microbacterium include Microbacterium ammoniaphilum. Examples of microorganisms belonging to the genus Brevibacterium include Brevibacterium formicum. Examples of microorganisms belonging to the genus Corynebacterium include Corynebacterium ammoniagenes. Examples of microorganisms belonging to the genus Pseudomonas include Pseudomonas putida.

[0199] When prokaryotes are used as hosts, vectors for introducing nucleic acids encoding recombinant proteins include, for example, pBTrp2 (manufactured by Boehringer Ingelheim), pGEX (manufactured by Pharmacia), pUC18, pBluescriptII, pSupex, pET22b, pCold, pUB110, and pNCO2 (Japanese Patent Application Publication No. 2002-238569).

[0200] Examples of eukaryotic hosts include yeast and filamentous fungi (molds, etc.). Examples of yeast include yeast belonging to the genera Saccharomyces, Pichia, and Schizosaccharomyces. Examples of filamentous fungi include filamentous fungi belonging to the genera Aspergillus, Penicillium, and Trichoderma.

[0201] When using eukaryotic cells as hosts, examples of vectors for introducing protein-encoding nucleic acids include YEP13 (ATCC 37115) and YEp24 (ATCC 37051). Any method for introducing an expression vector into such host cells can be used, as long as it is a method for introducing DNA into such host cells. Examples include methods using calcium ions [Proc. Natl. Acad. Sci. USA, 69, 2110 (1972)], electroporation, spheroplasting, protoplasting, lithium acetate, and competence assays.

[0202] As methods for expressing nucleic acids using a host transformed with an expression vector, in addition to direct expression, secretory production and fusion protein expression can be performed according to the methods described in Molecular Cloning, 2nd edition.

[0203] For example, a host transformed with an expression vector can be cultured in a culture medium to produce and accumulate the protein in the culture medium, and then collected from the culture medium to prepare the protein. The method for culturing the host in the culture medium can be carried out according to methods commonly used for host culture.

[0204] When the host is a prokaryotic organism such as Escherichia coli or a eukaryotic organism such as yeast, any culture medium may be used as long as it contains carbon sources, nitrogen sources, and inorganic salts that can be assimilated by the host and can efficiently culture the host. Both natural and synthetic culture media can be used.

[0205] As a carbon source, any substance assimilable to the above-mentioned transforming microorganisms may be used. For example, carbohydrates such as glucose, fructose, sucrose, and molasses containing these sugars, starch and starch hydrolysates, organic acids such as acetic acid and propionic acid, and alcohols such as ethanol and propanol can be used. As a nitrogen source, for example, inorganic acids such as ammonia, ammonium chloride, ammonium sulfate, ammonium acetate, and ammonium phosphate, ammonium salts of organic acids, other nitrogen-containing compounds, as well as peptone, meat extract, yeast extract, corn steep liquor, casein hydrolysate, soybean meal and soybean meal hydrolysate, various fermentation cells and their digestion products can be used. As inorganic salts, for example, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, magnesium phosphate, magnesium sulfate, sodium chloride, ferrous sulfate, manganese sulfate, copper sulfate, and calcium carbonate can be used.

[0206] Cultivation of prokaryotes such as Escherichia coli or eukaryotic organisms such as yeast can be carried out under aerobic conditions such as shaking culture or deep aeration stirring culture. The culture temperature is, for example, 15 to 40°C. The culture time is generally 16 hours to 7 days. The pH of the culture medium during cultivation is preferably maintained between 3.0 and 9.0. The pH of the culture medium can be adjusted using inorganic acids, organic acids, alkaline solutions, urea, calcium carbonate, ammonia, and the like.

[0207] Furthermore, antibiotics such as ampicillin and tetracycline may be added to the culture medium as needed during culturing. When culturing microorganisms transformed with expression vectors employing inducible promoters, inducers may be added to the culture medium as needed. For example, when culturing microorganisms transformed with expression vectors employing the lac promoter, isopropyl-β-D-thiogalactopyranoside may be added to the culture medium; and when culturing microorganisms transformed with expression vectors employing the trp promoter, indoleacrylic acid may be added to the culture medium.

[0208] The expressed protein can be isolated and purified by conventional methods. For example, when the protein is expressed in a dissolved state within the cells, after completion of the culture, the host cells are recovered by centrifugation, suspended in an aqueous buffer, and then disrupted using an ultrasonic disruptor, a French press, a Manton-Gaulin high-pressure homogenizer, a Dyno mill, or the like to obtain a cell-free extract. From the supernatant obtained by centrifuging the cell-free extract, a purified standard can be obtained by using methods commonly used for protein separation and purification, namely, solvent extraction, salting-out using ammonium sulfate or the like, desalting, precipitation using an organic solvent, anion exchange chromatography using resins such as diethylaminoethyl (DEAE)-agarose and DIAION HPA-75 (Mitsubishi Chemical Corporation), cation exchange chromatography using resins such as S-Sepharose FF (Pharmacia), hydrophobic chromatography using resins such as butyl agarose and phenyl agarose, gel filtration using molecular sieves, affinity chromatography, chromatofocusing, and electrophoresis such as isoelectric point electrophoresis, alone or in combination.

[0209] In addition, when the protein is expressed as an insoluble body within the cell, similarly, after the host cells are recovered, they are disrupted and centrifuged to recover the insoluble body of the protein in the form of a precipitate fraction. The recovered insoluble body of the protein can be solubilized using a protein denaturant. After performing this operation, a purified standard product of the protein can be obtained using the same separation and purification method as described above. When the protein is secreted outside the cell, the protein can be recovered from the culture supernatant. That is, the culture is treated using a method such as centrifugation to obtain a culture supernatant, and a purified standard product can be obtained from the culture supernatant using the same separation and purification method as described above.

[0210] [Hydrolysis process]

[0211] The preparation method described in this embodiment includes a process (hereinafter referred to as "hydrolysis process") of hydrolyzing the ester group by bringing the raw material molded body containing the protein esterified by the hydroxyl group into contact with an acidic or alkaline medium under a state of applying tension. It can be considered that when the hydrolysis is carried out under a state of applying tension, the penetration of the medium into the interior of the raw material molded body will be suppressed, so the ester group inside the raw material molded body is not easy to be removed or reduced, and only the ester group on the surface of the raw material molded body is easy to be removed or reduced. Even if only the ester group on the surface of such raw material molded body is removed or reduced, it is sufficient to suppress the situation where the ester group hydrolysis in the molded body produces a foul odor or the like. In addition, it can be inferred that the reduction in strength of the protein molded body is caused by the hydrolysis of the protein main chain inside the raw material molded body. Therefore, it can be considered that when the hydrolysis is carried out under a state of applying tension, the protein molded body can not only maintain sufficient strength, but also solve the problems caused by the esterification of the hydroxyl groups contained in the protein. In addition, when the hydrolysis is carried out under a state of applying tension, the toughness of the protein molded body (the area of ​​the region surrounded by stress (strength) and elongation in the stress (strength)-elongation curve) is improved.

[0212] In this embodiment, the tension is preferably such that the raw material molded body does not shrink due to contact with a medium (eg, aqueous solution). The tension can be applied by, for example, a filament winding (FW) method and can be adjusted by the applied load.

[0213] The tensile force at which the raw material molded body will not shrink due to contact with the medium can be determined, for example, by bringing the raw material molded body into contact with the medium while applying various tensile forces to the raw material molded body, and calculating the tensile force at which the size of the raw material molded body before and after contact with the medium (for example, when the raw material molded body is a fiber, it refers to the fiber length; when it is a heated and pressed molded body, a porous body and a gel, it refers to the volume; when it is a film, it refers to the area) changes by 87 to 113%, preferably 90 to 110%, more preferably 93 to 107%, and particularly preferably 95 to 105%.

[0214] For example, when the raw material molded body is a fiber (raw material fiber), the tensile force during treatment is preferably 150 MPa or less, more preferably 125 MPa or less, further preferably 100 MPa or less, and most preferably 75 MPa or less.

[0215] In this embodiment, the medium is an acidic or alkaline medium. The medium can be an alcohol solvent and an amine organic solvent that can perform ester solvent decomposition, but from the perspective of facilitating the implementation of a hydrolysis treatment that belongs to one type of solvent decomposition, it is preferably contained in water, more preferably an aqueous solution, water vapor, etc. The alkaline aqueous solution (medium) only needs to be alkaline, for example, it can be an alkaline aqueous solution with a pH value greater than 7. From the perspective of suppressing molecular chain hydrolysis and side reactions, it is preferably an alkaline aqueous solution with a pH value less than 12. The acidic aqueous solution (medium) only needs to be acidic, for example, it can be an acidic aqueous solution with a pH value less than 7. From the perspective of suppressing molecular chain hydrolysis and side reactions, it is preferably an acidic aqueous solution with a pH value greater than 1.

[0216] In this embodiment, as a method for performing hydrolysis, for example, a method of contacting the raw material molded body with an acidic or alkaline aqueous solution can be cited. In this case, the amount of the acidic or alkaline substance is preferably 0.1% by mass or more, more preferably 1.0% by mass or more, relative to the total amount of the protein solution.

[0217] The acidic substance that can be used for hydrolysis is not particularly limited and can be any of an inorganic acid or an organic acid. Examples of inorganic acids include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and boric acid. Examples of organic acids include carboxylic acid and sulfonic acid. Examples of the carboxylic acid include monocarboxylic acids such as formic acid, acetic acid, dichloroacetic acid, trifluoroacetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, caproic acid, caprylic acid, capric acid, and benzoic acid; saturated aliphatic carboxylic acids such as capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, cerotic acid, montanic acid, melissic acid, and cerorhyncholic acid; unsaturated aliphatic carboxylic acids such as undecylenic acid, oleic acid, elaidic acid, cetylene acid, erucic acid, brassylic acid, sorbic acid, linoleic acid, linolenic acid, arachidonic acid, propiolic acid, and stearic acid; and dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, undecanedioic acid, brassylic acid, maleic acid, fumaric acid, and glutaconic acid. The carboxylic acid may be in the form of an anhydride or an acid chloride. Examples of the sulfonic acid include methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid.

[0218] The alkaline substance that can be used for hydrolysis is not particularly limited as long as it is soluble in water, and can be any inorganic base or organic base. The inorganic base is not particularly limited as long as it is soluble in water. Examples of the inorganic base include potassium hydroxide, sodium hydroxide, sodium bicarbonate, and sodium carbonate. Examples of the organic base include alkylamines such as ammonia, methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, and triethylamine; and primary to tertiary amines such as aminoethanol, methylaminoethanol, dimethylaminoethanol, ethylaminoethanol, diethylaminoethanol, and diethanolamine.

[0219] The hydrolysis of ester groups is an equilibrium reaction. Although the same acid as that generated when the ester group is cleaved can be used as the acid required for the hydrolysis, it is preferred not to use such an acid.

[0220] In this embodiment, the hydrolysis is performed under acidic or alkaline conditions, preferably acidic conditions with a pH value of 1 to 6 or alkaline conditions with a pH value of 8 to 14, and can be adjusted by the acidic or alkaline substance used.

[0221] In the present embodiment, when an alkaline aqueous solution is used, the pH value is preferably greater than 8 and less than 12 for reasons described below.

[0222] When using an alkaline aqueous solution, the carboxylic acid dissociates by hydrolysis to form a carboxylate anion. At this time, the electrophilicity is lost, so the reverse reaction is less likely to occur. From this point of view, an alkaline aqueous solution (medium) is more preferable than an acidic one. From the perspective of showing high reactivity even without heating, the pH value of the alkaline aqueous solution is preferably 8 to 14; from the perspective of the hydrolysis reaction rate, the pH value is preferably greater than 8. In addition, when the raw material composition is a molded body, in a strongly alkaline environment, from the perspective of keeping molecular chain breakage such as dispersion destruction and amide hydrolysis to a minimum, the pH value is preferably less than 12.

[0223] Since the hydrolysis of ester groups proceeds rapidly in an acidic or alkaline aqueous solution, the reaction time is not limited, but is preferably longer than 1 minute from the viewpoint of sufficient removal of the ester groups.

[0224] In this embodiment, the hydrolysis temperature is not particularly limited, but may be, for example, 5° C. or higher, 10° C. or higher, 20° C. or higher, 30° C. or higher, or 80° C. or higher. Furthermore, the hydrolysis temperature may be, for example, 90° C. or lower, 80° C. or lower, 50° C. or lower, 40° C. or lower, or 35° C. or lower.

[0225] In this embodiment, the shaped body removed from the aqueous solution used for hydrolysis may contain residual acidic or alkaline substances, which may cause molecular chain scission. To prevent such molecular chain scission, the method for preparing the protein shaped body may further include a step of removing the residual acidic or alkaline substances. For example, the step of removing the residual acidic or alkaline substances includes washing the shaped body with water.

[0226] (Method for producing raw material molded body)

[0227] In this embodiment, the method for preparing the raw material molded body is not particularly limited, and for example, the method may include the following steps.

[0228] [Dissolution process]

[0229] The solubilization step is a step of dissolving the protein in a solvent (for example, a carboxylic acid such as formic acid) to obtain a protein solution.

[0230] In the solubilization step, the protein to be solubilized (hereinafter also referred to as the "target protein") can be a purified protein or a protein in a host cell expressing the protein (recombinant protein). The purified protein can be a protein purified from a host cell expressing the protein. When a protein in a host cell is solubilized as the target protein, the host cell is brought into contact with a solvent, and the protein in the host cell is dissolved in the solvent. The host cell can be any host cell as long as it expresses the target protein, and can be, for example, intact cells or cells that have been subjected to a disruption treatment or the like. In addition, cells that have undergone a simple purification treatment can also be used.

[0231] The method for purifying a protein from a host cell expressing the protein is not particularly limited, and for example, the methods described in Japanese Patent Nos. 6077570 and 6077569 can be used.

[0232] When a carboxylic acid such as formic acid is used as a solvent in the dissolution step, the hydroxyl groups in the protein undergo a dehydration condensation reaction with the carboxylic acid to produce an esterified protein. As carboxylic acids, for example, monocarboxylic acids such as formic acid, acetic acid, dichloroacetic acid, trifluoroacetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, caproic acid, caprylic acid, capric acid, and benzoic acid; saturated aliphatic carboxylic acids such as capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, cerotic acid, montanic acid, melissic acid, and cerorhyncholic acid; unsaturated aliphatic carboxylic acids such as undecylenic acid, oleic acid, elaidic acid, cetyl esters, erucic acid, brassylic acid, sorbic acid, linoleic acid, linolenic acid, arachidonic acid, propiolic acid, and stearic acid; and dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, undecanedioic acid, brassylic acid, maleic acid, fumaric acid, and glutaconic acid can be used. The carboxylic acid may be in the form of anhydride or acid chloride.

[0233] The dissolution process can be carried out at room temperature or maintained at various heating temperatures to dissolve the protein in the solvent. The holding time at the heating temperature is not particularly limited and can be 10 minutes or longer. Considering industrial production, it is preferably 10 to 120 minutes, more preferably 10 to 60 minutes, and even more preferably 10 to 30 minutes. The holding time at the heating temperature can be appropriately set so that the protein is fully dissolved and the amount of inclusions (substances other than the target protein) dissolved is minimal.

[0234] The amount of the solvent added to dissolve the protein is not particularly limited as long as it is an amount capable of dissolving the protein.

[0235] When dissolving purified protein, the amount of solvent added is calculated based on the ratio of solvent volume (mL) to protein (dry powder containing protein) weight (g) (volume (mL) / weight (g)), and can be 1 to 100 times, 1 to 50 times, 1 to 25 times, 1 to 10 times, or 1 to 5 times.

[0236] When solubilizing the protein in the host cells expressing the protein, the amount of solvent added is calculated as the ratio of solvent (mL) to host cell weight (g) (volume (mL) / weight (g)), and can be 1 to 100 times, 1 to 50 times, 1 to 25 times, 1 to 10 times, or 1 to 5 times.

[0237] The solvent may contain inorganic salts. Adding inorganic salts to the solvent can increase the solubility of the protein.

[0238] Examples of the inorganic salt that can be added to the solvent include alkali metal halides, alkaline earth metal halides, alkaline earth metal nitrates, thiocyanates, and perchlorates.

[0239] Examples of the alkali metal halide include potassium bromide, sodium bromide, lithium bromide, potassium chloride, sodium chloride, lithium chloride, sodium fluoride, potassium fluoride, cesium fluoride, potassium iodide, sodium iodide, and lithium iodide.

[0240] Examples of the alkaline earth metal halide include calcium chloride, magnesium chloride, magnesium bromide, calcium bromide, magnesium iodide, and calcium iodide.

[0241] Examples of the alkaline earth metal nitrate include calcium nitrate, magnesium nitrate, strontium nitrate, and barium nitrate.

[0242] Examples of the thiocyanate include sodium thiocyanate, ammonium thiocyanate, and guanidine thiocyanate.

[0243] Examples of the perchlorate include ammonium perchlorate, potassium perchlorate, calcium perchlorate, silver perchlorate, sodium perchlorate, and magnesium perchlorate.

[0244] These inorganic salts may be used alone or in combination of two or more.

[0245] Preferred inorganic salts include alkali metal halides and alkaline earth metal halides. Specific examples of preferred inorganic salts include lithium chloride and calcium chloride.

[0246] The amount (content) of the inorganic salt added may be 0.5% by mass or more and 10% by mass or less, or 0.5% by mass or less and 5% by mass or less, relative to the total mass of the solvent.

[0247] Insoluble matter can be removed from the protein solution as needed. Specifically, the method for preparing the raw material molded body can, after the dissolution step, optionally include a step for removing insoluble matter from the protein solution. Typical methods for removing insoluble matter from the protein solution include centrifugation, filtration using filters such as drum filters and press filters. When using filtration, the simultaneous use of filter aids such as cerium silica and diatomaceous earth, as well as pre-coating agents, can more effectively remove insoluble matter from the protein solution.

[0248] The protein solution contains protein and a solvent that dissolves the protein (dissolving solvent). The protein solution may contain impurities contained with the protein during the dissolution step. The protein solution may be a solution for forming a protein molded body.

[0249] The protein content in the protein solution may be 5% by mass or more and 35% by mass or less, or 5% by mass or less and 50% by mass or less, relative to the total amount of the protein solution.

[0250] The method for producing a protein in which a hydroxyl group is esterified is not particularly limited. The method may be a method in which a carboxylic acid such as formic acid is used as a solvent in the dissolution step, or a method in which the protein is produced without the dissolution step. For example, the method may be a method in which at least one selected from carboxylic acids, acid anhydrides, and acid chlorides is reacted with a protein having a hydroxyl group such as serine, tyrosine, or threonine.

[0251] [Molding process]

[0252] The molding step is a step of molding the raw material molded body using the protein solution. The shape of the raw material molded body is not particularly limited, and examples thereof include fibers, heat-pressed molded bodies, films, porous bodies, gels, and resins.

[0253] The protein concentration and viscosity of the protein solution can be preferably adjusted by adjusting the raw material shaped body to be shaped.

[0254] The method for adjusting the protein concentration in the protein solution is not particularly limited. Examples thereof include a method of increasing the protein concentration by volatilizing the solvent by distillation, a method of using a substance with a high protein concentration in the dissolution step, or a method of reducing the amount of solvent added relative to the amount of protein.

[0255] The viscosity suitable for spinning is generally 10 to 50,000 cP (centipoise). The viscosity can be measured, for example, using an EMS viscometer manufactured by Kyoto Electronics Industry Co., Ltd. If the viscosity of the protein solution is not within the range of 10 to 10,000 cP (centipoise), the viscosity of the protein solution can be adjusted to a viscosity suitable for spinning. The viscosity can be adjusted using the methods described above. The solvent may contain the preferred inorganic salts listed above.

[0256] When the raw material molded body to be formed is a fiber (raw material fiber), the protein content (concentration) in the protein solution can be adjusted to a concentration and viscosity that can be spun as needed. The method for adjusting the protein concentration and viscosity is not particularly limited. In addition, as a spinning method, wet spinning and the like can be cited. After the protein solution adjusted to a concentration and viscosity suitable for spinning is added to the coagulation liquid as a doping liquid, the protein coagulates. At this time, by adding the protein solution as a filamentous liquid to the coagulation liquid, the protein can be coagulated into a filament and form a filament (undrawn filament). The undrawn filament can be formed, for example, according to the method described in Japanese Patent Gazette No. 5584932.

[0257] An example of wet spinning is shown below, but the spinning method is not particularly limited and may be dry spinning or wet spinning.

[0258] Wet spinning-stretching

[0259] (a) Wet spinning

[0260] The coagulation liquid can be any solution capable of removing the solvent. A lower alcohol having 1 to 5 carbon atoms, such as methanol, ethanol, or 2-propanol, or acetone is preferably used as the coagulation liquid. The coagulation liquid may contain water. From the perspective of spinning stability, the coagulation liquid temperature is preferably 5 to 30°C.

[0261] There is no particular limitation on the method of adding the protein solution as a filamentous liquid. For example, a method of extruding the protein solution from a spinning spinneret into the coagulation liquid in the desolventizing tank can be cited. After the protein coagulates, an undrawn filament is obtained. The extrusion speed when the protein solution is extruded into the coagulation liquid can be appropriately set according to the spinneret diameter and the viscosity of the protein solution. For example, when using a syringe pump with a nozzle with a diameter of 0.1 to 0.6 mm, the extrusion speed is preferably 0.2 to 6.0 mL / h per hole, and more preferably 1.4 to 4.0 mL / h per hole from the perspective of spinning stability. The length of the desolventizing tank (coagulation liquid tank) containing the coagulation liquid is not particularly limited. For example, the length can be 200 to 500 mm. The collection speed of the undrawn filament formed by protein coagulation can be, for example, 1 to 14 m / min, and the stagnation time can be, for example, 0.01 to 0.15 min. From the perspective of desolventizing efficiency, the collection speed of the undrawn filament is preferably 1 to 3 m / min. The unstretched yarn formed by protein coagulation can be further stretched in a coagulation solution (pre-stretching). However, from the perspective of suppressing evaporation of the lower alcohol used in the coagulation solution, it is preferable to maintain the coagulation solution at a low temperature and collect the unstretched yarn from the coagulation solution.

[0262] (b) Stretching

[0263] The undrawn yarn obtained by the above method may also be further drawn. The drawing process may be a single-stage drawing process or a multi-stage drawing process of two or more stages. Multi-stage drawing can achieve multi-stage molecular orientation and increase the total draw ratio, making it suitable for producing high-tenacity fibers.

[0264] During wet spinning, the raw fiber can be treated to prevent shrinkage. Examples of shrinkage-proofing methods include: exposing the protein fiber, which has not yet come into contact with water, to water after spinning to induce irreversible shrinkage (hydroshrinkage method); and heating the protein fiber, which has not yet come into contact with water, after spinning to relax the heated protein fiber and induce irreversible shrinkage (dry heat shrinkage method).

[0265] The irreversible shrinkage of protein fibers is believed to be caused by, for example, the following reasons. Specifically, one reason is believed to be the secondary or tertiary structure of the protein fibers, and another reason is the relaxation of residual stress in the protein fibers caused by, for example, stretching during the production process.

[0266] The water shrinkage method includes a process (shrinkage process) in which the protein fiber, which has not yet been in contact with water, is brought into contact with water after spinning to cause irreversible shrinkage. In this shrinkage process, the protein fiber shrinks without being affected by external forces by contact with water. The water in contact can be water in any state of liquid or gas. The method of bringing the protein fiber into contact with water is not particularly limited. For example, the following methods can be listed: a method of immersing the protein fiber in water, a method of spraying water on the protein fiber in a state of steam at room temperature or after heating, a method of exposing the protein fiber to a high humidity environment filled with water vapor, etc. Among these methods, the method of immersing the protein fiber in water is preferred because it can effectively shorten the shrinkage time and simplify the processing equipment. As the method of immersing the protein fiber in water, specifically, for example, there is a method of putting the protein fiber into a container filled with water at a specified temperature and bringing it into contact with water, etc.

[0267] The temperature of the water in contact with the protein fibers is not particularly limited; for example, it is preferably below the boiling point. At this temperature, workability and the workability of the shrinking process can be improved. Furthermore, the upper limit of the water temperature is preferably 90°C or lower, more preferably 80°C or lower. The lower limit of the water temperature is preferably 10°C or higher, more preferably 40°C or higher, and even more preferably 70°C or higher. The temperature of the water in contact with the protein fibers can be adjusted depending on the fibers that constitute the protein fibers. Furthermore, the water temperature can be fixed or varied to a specified temperature while the water is in contact with the protein fibers.

[0268] The time for which the protein fibers are in contact with water is not particularly limited, and for example, it can be at least 1 minute. This time can be at least 10 minutes, at least 20 minutes, or even at least 30 minutes. Furthermore, there is no particular upper limit to this time, but from the perspective of shortening the preparation process and eliminating the possibility of hydrolysis of the protein fibers, it can be, for example, 120 minutes or less, 90 minutes or less, or even 60 minutes or less.

[0269] The hydroshrinkage method may further include a step of bringing the protein fibers into contact with water and then drying them (drying step) after the shrinking step.

[0270] The drying method in the drying process is not particularly limited. For example, it can be natural drying or forced drying using a drying device. The drying temperature is not limited as long as it is lower than the temperature at which the protein is thermally damaged. It is generally a temperature in the range of 20 to 150°C, preferably a temperature in the range of 40 to 120°C, and more preferably a temperature in the range of 60 to 100°C. Within this temperature range, the protein will not be thermally damaged, and the protein fiber can be dried more quickly and efficiently. The drying time can be appropriately selected according to the drying temperature, for example, a time that can eliminate the influence of excessive drying of the protein fiber on the quality and physical properties of the braid can be used.

[0271] The dry heat shrinking method includes the following steps: a step of heating the protein fibers that have not yet come into contact with water after spinning (heating step); and a step of relaxing the heated protein fibers to cause irreversible shrinkage (relaxation shrinkage step).

[0272] During the heating step, the heating temperature is preferably above the softening temperature of the protein used in the protein fibers. The protein softening temperature, as used herein, refers to the temperature at which protein fibers begin to shrink due to stress relaxation. During relaxation shrinkage by heating above the protein softening temperature, the fibers shrink to a degree that cannot be achieved by simply escaping moisture from the fibers. As a result, shrinkage, or dimensional change, of the resulting protein fibers upon contact with water is substantially suppressed. The heating temperature is preferably 80°C or higher, more preferably 180°C to 280°C, even more preferably 200°C to 240°C, and even more preferably 220°C to 240°C.

[0273] From the perspective of fiber elongation after heat treatment, the heating time in the heating step is preferably 60 seconds or less, more preferably 30 seconds or less, and even more preferably 5 seconds or less. It is believed that the length of the heating time has little effect on stress.

[0274] In the relaxation and shrinking step, the relaxation ratio is preferably greater than 1, more preferably 1.4, further preferably 1.7, and particularly preferably 2. The relaxation ratio can be determined, for example, by the ratio of the protein fiber delivery speed to the winding speed.

[0275] When the raw material molded body is a heated and pressed molded body (raw material heated and pressed molded body), the method for forming the raw material heated and pressed molded body is not particularly limited. For example, after adding dry protein powder to a press molding machine, pressurizing and heating using a hand press or the like can reach the temperature required for drying the protein powder, thereby obtaining a heated and pressed molded body. In addition, the raw material heated and pressed molded body can be formed according to the method described in Japanese patent documents (Japanese Patent Application No. 2017-539869, PCT / JP2016 / 076500).

[0276] When the raw material formed article is a film (raw material film), the protein solution can be adjusted to a concentration and viscosity suitable for film formation, as needed. The method for forming the protein into a film is not particularly limited, and examples thereof include coating the protein solution at a predetermined thickness on a solvent-resistant flat plate to form a coating film, and then removing the solvent from the coating film to obtain a film of predetermined thickness.

[0277] As a method for forming a film of a predetermined thickness, for example, a film casting method can be cited. When forming a film using the film casting method, a protein solution is cast onto a flat plate using a fixture such as a coater or a blade coater to form a film having a thickness of several microns or more. The film is then dried under reduced pressure or immersed in a desolventizing tank to remove the solvent, thereby obtaining a protein film (polypeptide film). The raw film can be formed according to the method described in Japanese Patent No. 5678283.

[0278] When the raw material shaped body is a porous body (raw material porous body), the concentration and viscosity can be adjusted as needed to achieve porosification. The method for forming the raw material porous body is not particularly limited. For example, the following methods can be used: adding an appropriate amount of a foaming agent to a protein solution adjusted to a concentration and viscosity suitable for porosification, removing the solvent, and obtaining the porous body; or, alternatively, the method described in Japanese Patent No. 5796147 can be used.

[0279] When the raw material shaped body is a gel (raw material gel), the method for forming the raw material gel is not particularly limited. For example, the raw material gel can be obtained by dissolving the dried protein in a dissolving solvent to obtain a polypeptide solution, followed by replacing the solution generated in the solution generation step with a water-soluble solvent. In this case, a step of casting the product into a mold and forming it into a predetermined shape can be added between the solution generation step and the step of replacing the dissolving solvent with a water-soluble solvent, or the product can be cut into a predetermined shape after the step of replacing the dissolving solvent with a water-soluble solvent. Furthermore, the raw material gel can be formed according to the method described in Japanese Patent No. 5782580.

[0280] When the raw material molded body is a resin (raw material resin), the protein solution can be adjusted to a concentration and viscosity that allows resinification as needed. The method for forming the raw material resin is not particularly limited and can be prepared according to the method described in Japanese Patent No. 5678283.

[0281] [Processing method of protein molded body]

[0282] The method for processing a shaped protein product according to this embodiment includes the step of hydrolyzing the ester groups by bringing the shaped protein product containing a protein having esterified hydroxyl groups into contact with an acidic or alkaline medium while applying tension.

[0283] In this embodiment, the protein with esterified hydroxyl groups, the magnitude of the pulling force, the method of applying the pulling force, the nature of the acidic or alkaline medium, and the method of hydrolyzing the ester groups are applicable to the same embodiments as those described in the above-mentioned method for producing the protein shaped body. The protein shaped body can be obtained by a method that includes the step of hydrolyzing the ester groups (hydrolysis step) described in the above-mentioned method for producing the protein shaped body, or it can be obtained by a method that does not include the hydrolysis step.

[0284] The processing method described in this embodiment can re-expose the hydroxyl groups in the protein, and thus can provide a processing method for a protein molded body that can not only maintain sufficient strength but also solve the problems caused by the esterification of the hydroxyl groups contained in the protein.

[0285] [Example]

[0286] Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples.

[0287] (Protein Preparation)

[0288] (1) Preparation of expression vector

[0289] Spider silk fibroin having SEQ ID NO: 40 (hereinafter also referred to as "PRT966") was designed based on the base sequence and amino acid sequence of fibroin derived from the gold-spinning spider (Nephila clavipes) (GenBank Accession Nos.: P46804.1, GI: 1174415).

[0290] Next, a nucleic acid encoding the designed protein (spider silk fibroin) was synthesized. An NdeI site was added to the 5' end of the nucleic acid, and an EcoRI site was added downstream of the stop codon. This nucleic acid was cloned into a cloning vector (pUC118). The nucleic acid was then treated with restriction enzymes NdeI and EcoRI, excised, and recombined into the protein expression vector pET-22b(+) to obtain an expression vector.

[0291] (2) Protein expression

[0292] The expression vector obtained in (1) was used to transform E. coli BLR (DE3). The transformed E. coli was cultured in 2 mL LB medium containing ampicillin for 15 hours. The culture solution was added to 100 mL seed culture medium (Table 4) containing ampicillin to make the OD 600 The culture temperature was maintained at 30°C and the flask culture was continued until the OD 600 When the temperature reaches 5 (about 15 hours), a seed culture solution is obtained.

[0293] [Table 4]

[0294] Planted in culture medium

[0295]

[0296] The seed culture was added to a fermenter containing 500 mL of production medium (Table 5) to obtain an OD 600 The culture medium temperature was maintained at 37°C and the pH was kept constant at 6.9. In addition, the dissolved oxygen concentration in the culture medium was maintained at 20% of the saturated dissolved oxygen concentration.

[0297] [Table 5]

[0298] Production medium

[0299]

[0300] After the glucose in the production medium is completely consumed, the feed solution (glucose 455g / 1L, yeast extract 120g / 1L) is immediately added at a rate of 1mL / min. The culture temperature is maintained at 37°C and the pH value is constantly controlled at 6.9 for cultivation. In addition, the dissolved oxygen concentration in the culture solution is maintained at 20% of the dissolved oxygen saturation concentration and cultured for 20 hours. Then, 1M isopropyl-β-thiogalactopyranoside (IPTG) is added to the culture solution to make its final concentration 1mM, and the induced modified silk core protein is expressed. After 20 hours after the addition of IPTG, the culture solution is centrifuged and the bacteria are recovered. SDS-PAGE is performed using bacteria prepared from the culture solution before and after the addition of IPTG, and the expression of the target protein (spider silk core protein) is confirmed by the appearance of the band of the target recombinant protein depending on the addition of IPTG.

[0301] (3) Protein purification

[0302] Two hours after adding IPTG, the recovered cells were washed with 20 mM Tris-HCl buffer (pH 7.4). The washed cells were suspended in 20 mM Tris-HCl buffer (pH 7.4) containing approximately 1 mM PMSF and disrupted using a high-pressure homogenizer (GFA Naniro Soavi). The disrupted cells were centrifuged to obtain a precipitate. The resulting precipitate was washed with 20 mM Tris-HCl buffer (pH 7.4) until it reached high purity. The washed precipitate was suspended in 8 M guanidine buffer (8 M guanidine hydrochloride, 10 mM sodium dihydrogen phosphate, 20 mM NaCl, 1 mM Tris-HCl, pH 7.0) to a concentration of 100 mg / mL and stirred at 60°C for 30 minutes to dissolve the cell. After dissolution, the cell was dialyzed against water using dialysis tubing (Sanko Junyaku Co., Ltd., Cellulose Tubing 36 / 32). The white aggregated protein obtained after dialysis was recovered by centrifugation, and the water content was removed by a freeze dryer. The freeze-dried powder was then recovered to obtain the protein (spider silk fibroin).

[0303] (4) Preparation of raw fiber

[0304] Spider silk fibroin dry powder was dissolved in formic acid and filtered through a metal filter with a pore size of 1 μm to obtain a dope solution (protein concentration in the dope solution: 30% by mass). Using a known spinning apparatus, the dope solution was discharged into a coagulation solution via a gear pump. The spinning conditions were as follows. This yielded raw material fibers (raw material spider silk fibroin fibers).

[0305] (Spinning Conditions)

[0306] Nozzle aperture: 0.1mm

[0307] Coagulation liquid: methanol

[0308] Coagulation liquid temperature: 25℃

[0309] Water cleaning bath temperature: 25°C

[0310] Hot roller temperature: 60°C

[0311] (5) Hydrolysis treatment

[0312] The raw fiber obtained in (4) is hydrolyzed according to the following steps [i] to [iii].

[0313] [i] Immerse the raw material fiber in an alkaline aqueous solution and stir.

[0314] [ii] The raw material fiber is washed with tap water to a pH of 8.0 or less.

[0315] [iii] The raw fiber was dried naturally for two days.

[0316] Table 6 shows the processing conditions in step [i]. In Example 1, a wire winding machine FWM-1500LF (manufactured by Asahi Kasei Engineering Corporation) was used to wind the raw fiber (winding width: 20 cm, number of layers: 20 ply) while applying tension (load: 10 N) to a 300 × 300 × 2 (mm) stainless steel plate.

[0317] [Table 6]

[0318]

[0319] (6) Each fiber obtained in the evaluation of formyl residue (formate group) removal by FT-IR (5) was measured by the ATR method (total reflection method) using a Fourier transform infrared spectrophotometer (Nicolet iS50 FT-IR, manufactured by Thermo Fisher Scientific Co., Ltd.) to evaluate the removal of formyl residues. The IR spectrum of each fiber (Example 1 (n=4) and Comparative Example 1) was confirmed to have a wave number of 1730 cm -1 (Peak belonging to formyl residue C=O, Figure 4 The peak height of the arrow in the middle is used to evaluate whether the peak is detected ( Figure 4 If no peak is detected, it is determined that the formyl residue has been removed. In addition, a sample that was not subjected to the hydrolysis treatment (5) above was used as a control.

[0320] pass Figure 4 It was confirmed that the hydrolysis of the raw material fibers with an alkaline aqueous solution caused the formyl residues to undergo a hydrolysis reaction, and thus the formyl residues in the protein fibers were removed (Example 1 and Comparative Example 1).

[0321] In the FT-IR spectrum ( Figure 4 ) was fitted with the Lorentzian function, and the peak (1470 cm -1 The area ratio of the peak due to formate to the area of ​​the reference peak was determined (area ratio). The area ratio in Example 1 was determined and compared with the area ratio in the control to calculate the formyl residue ratio [%] in Example 1. The results are shown in Table 7.

[0322] [Table 7]

[0323]

[0324] Furthermore, assuming that all hydroxyl groups were formylated before treatment, by multiplying the hydroxyl group count in spider silk fibroin (1.88 mmol / g) by the proportion of formyl residues (27.89%), we can calculate that the undeformylated portion is 0.52 mmol / g. Using this calculation result, the deformylated portion can be calculated as 1.36 mmol / g (=1.88 mmol / g - 0.52 mmol / g).

[0325] (7) Evaluation of elongation

[0326] Each hydrolyzed and dried fiber was fixed to a clamp with a fiber length of 20 mm. The stress (strength) and elongation were measured using a single fiber tensile testing machine FAVIMAT+ manufactured by Textechno at a tensile speed of 10 mm / min under the conditions of a load cell capacity of 2 N, a pretension of 1.25 cmN / tex, a temperature of 20°C, and a relative humidity of 65%. The results are as follows: Figure 5 shown.

[0327] Comparison of Example 1 with Comparative Example 1 shows that applying tension during hydrolysis can increase the strength of protein fibers. Furthermore, comparison of the control with Example 1 shows that applying tension during hydrolysis increases elongation, thereby improving the toughness (the area encompassed by stress (strength) and elongation) of protein fibers. Sequence Listing <110> Spiber Co., Ltd. <120> A method for preparing a protein shaped body <130> 19PS059WO1 <160> 44 <170> PatentIn version 3.5 <210> 1 <211> 50 <212> PRT <213> Cross Garden Spider <400> 1 Ser Gly Cys Asp Val Leu Val Gln Ala Leu Leu Glu Val Val Ser Ala 1 5 10 15 Leu Val Ser Ile Leu Gly Ser Ser Ser Ile Gly Gln Ile Asn Tyr Gly 20 25 30 Ala Ser Ala Gln Tyr Thr Gln Met Val Gly Gln Ser Val Ala Gln Ala 35 40 45 Leu Ala 50 <210> 2 <211> 30 <212> PRT <213> Araneus diadematus <400> 2 Ser Gly Cys Asp Val Leu Val Gln Ala Leu Leu Glu Val Val Ser Ala 1 5 10 15 Leu Val Ser Ile Leu Gly Ser Ser Ser Ile Gly Gln Ile Asn 20 25 30 <210> 3 <211> 21 <212> PRT <213> Araneus diadematus <400> 3 Ser Gly Cys Asp Val Leu Val Gln Ala Leu Leu Glu Val Val Ser Ala 1 5 10 15 Leu Val Ser Ile Leu 20 <210> 4 <211> 1154 <212> PRT <213> Artificial Sequence <220> <223> Recombinant spider silk protein ADF3KaiLargeNRSH1 <400> 4 Met His His His His His His His His His His Ser Ser Gly Ser Ser 1 5 10 15 Leu Glu Val Leu Phe Gln Gly Pro Ala Arg Ala Gly Ser Gly Gln Gln 20 25 30 Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly 35 40 45 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Gly Gly Tyr 50 55 60 Gly Pro Gly Ser Gly Gln Gln Gly Pro Ser Gln Gln Gly Pro Gly Gln 65 70 75 80 Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 85 90 95 Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ser Gly Gln Gln Gly Pro 100 105 110 Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 115 120 125 Ala Gly Gly Asn Gly Pro Gly Ser Gly Gln Gln Gly Ala Gly Gln Gln 130 135 140 Gly Pro Gly Gln Gln Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala 145 150 155 160 Gly Gly Tyr Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly 165 170 175 Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala 180 185 190 Ala Ala Gly Gly Tyr Gly Pro Gly Ser Gly Gln Gly Pro Gly Gln Gln 195 200 205 Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 210 215 220 Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly 225 230 235 240 Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly 245 250 255 Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly 260 265 270 Tyr Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro 275 280 285 Tyr Gly Pro Gly Ala Ser Ala Ala Ser Ala Ala Ser Gly Gly Tyr Gly 290 295 300 Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly Gln 305 310 315 320 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Gly Gly 325 330 335 Tyr Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly 340 345 350 Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly 355 360 365 Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly 370 375 380 Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro 385 390 395 400 Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly 405 410 415 Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly 420 425 430 Gln Gly Ala Tyr Gly Pro Gly Ala Ser Ala Ala Ala Gly Ala Ala Gly 435 440 445 Gly Tyr Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro 450 455 460 Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly 465 470 475 480 Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly 485 490 495 Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly 500 505 510 Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro 515 520 525 Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ser Ala Ala Val Ser 530 535 540 Val Ser Arg Ala Arg Ala Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln 545 550 555 560 Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly 565 570 575 Ala Ser Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ser Gly 580 585 590 Gln Gln Gly Pro Ser Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly 595 600 605 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Gly 610 615 620 Gly Tyr Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro 625 630 635 640 Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Gly Gly Asn Gly 645 650 655 Pro Gly Ser Gly Gln Gln Gly Ala Gly Gln Gln Gly Pro Gly Gln Gln 660 665 670 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro 675 680 685 Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly Gln Gly 690 695 700 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Gly Gly Tyr 705 710 715 720 Gly Pro Gly Ser Gly Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly Gln 725 730 735 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Gly Gly 740 745 750 Tyr Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly 755 760 765 Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala 770 775 780 Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Tyr Gly Gln Gln Gly 785 790 795 800 Pro Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala 805 810 815 Ser Ala Ala Ser Ala Ala Ser Gly Gly Tyr Gly Pro Gly Ser Gly Gln 820 825 830 Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro 835 840 845 Gly Ala Ser Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ser 850 855 860 Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly 865 870 875 880 Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala 885 890 895 Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ser Gly Gln Gln Gly 900 905 910 Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro 915 920 925 Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly 930 935 940 Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly Gln Gly Ala Tyr Gly 945 950 955 960 Pro Gly Ala Ser Ala Ala Ala Gly Ala Ala Gly Gly Tyr Gly Pro Gly 965 970 975 Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro 980 985 990 Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly 995 1000 1005 Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser 1010 1015 1020 Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ser Gly Gln 1025 1030 1035 Gln Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly 1040 1045 1050 Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ser Ala Ala Val Ser Val 1055 1060 1065 Gly Gly Tyr Gly Pro Gln Ser Ser Ser Val Pro Val Ala Ser Ala 1070 1075 1080 Val Ala Ser Arg Leu Ser Ser Pro Ala Ala Ser Ser Arg Val Ser 1085 1090 1095 Ser Ala Val Ser Ser Leu Val Ser Ser Gly Pro Thr Lys His Ala 1100 1105 1110 Ala Leu Ser Asn Thr Ile Ser Ser Val Val Ser Gln Val Ser Ala 1115 1120 1125 Ser Asn Pro Gly Leu Ser Gly Cys Asp Val Leu Val Gln Ala Leu 1130 1135 1140 Leu Glu Val Val Ser Ala Leu Val Ser Ile Leu 1145 1150 <210> 5 <211> twenty four <212> PRT <213> Artificial sequence <220> <223> His tag and start codon <400> 5 Met His His His His His His His His His Ser Ser Gly Ser Ser 1 5 10 15 Leu Glu Val Leu Phe Gln Gly Pro 20 <210> 6 <211> 597 <212> PRT <213> Artificial sequence <220> <223> Met-PRT380 <400> 6 Met Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Gly Gln Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly 20 25 30 Gln Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly 35 40 45 Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro 50 55 60 Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala 65 70 75 80 Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser Ala Ala 85 90 95 Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln 100 105 110 Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly 115 120 125 Pro Gly Gln Gln Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly Pro 130 135 140 Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala 145 150 155 160 Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 165 170 175 Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly 180 185 190 Gln Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly 195 200 205 Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala 210 215 220 Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr 225 230 235 240 Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly 245 250 255 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Tyr Gly Pro 260 265 270 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala 275 280 285 Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly 290 295 300 Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro 305 310 315 320 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro 325 330 335 Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro Gly Ser Ser Ala Ala Ala 340 345 350 Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala 355 360 365 Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly 370 375 380 Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro 385 390 395 400 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala 405 410 415 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 420 425 430 Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala 435 440 445 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln Tyr 450 455 460 Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly 465 470 475 480 Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 485 490 495 Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro 500 505 510 Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Tyr Gly 515 520 525 Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Asn Gly Pro Gly Ser 530 535 540 Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala Ala Ala 545 550 555 560 Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly 565 570 575 Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln 580 585 590 Gly Pro Gly Ala Ser 595 <210> 7 <211> 590 <212> PRT <213> Synthetic Sequence <220> <223> Met-PRT410 <400> 7 Met Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Gly Gln Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly 20 25 30 Gln Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly 35 40 45 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro 50 55 60 Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 65 70 75 80 Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly Gln Tyr Gly Pro Gly Gln 85 90 95 Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 100 105 110 Gly Gln Tyr Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Ser Ala 115 120 125 Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr 130 135 140 Gly Pro Gly Ala Ser Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly 145 150 155 160 Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro 165 170 175 Gly Gln Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr 180 185 190 Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly 195 200 205 Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala 210 215 220 Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser 225 230 235 240 Ala Ala Ala Ala Ala Gly Gln Tyr Gly Tyr Gly Pro Gly Gln Gln Gly 245 250 255 Pro Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln 260 265 270 Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala 275 280 285 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 290 295 300 Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Tyr Gly 305 310 315 320 Pro Gly Ser Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser 325 330 335 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 340 345 350 Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln 355 360 365 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly 370 375 380 Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 385 390 395 400 Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala 405 410 415 Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr 420 425 430 Gly Pro Gly Gln Ser Gly Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro 435 440 445 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro 450 455 460 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala 465 470 475 480 Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly 485 490 495 Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser 500 505 510 Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly 515 520 525 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly 530 535 540 Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser 545 550 555 560 Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala 565 570 575 Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser 580 585 590 <210> 8 <211> 565 <212> PRT <213> Artificial Sequence <220> <223> Met-PRT525 <400> 8 Met Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Gly Ser Asn Gly Pro Gly Ser Gly Gln Gln Gly 20 25 30 Pro Gly Gln Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln 35 40 45 Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly 50 55 60 Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala 65 70 75 80 Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly 85 90 95 Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser 100 105 110 Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly 115 120 125 Gln Gln Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro 130 135 140 Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly 145 150 155 160 Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala 165 170 175 Ala Ala Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly Gln Tyr Gly 180 185 190 Pro Tyr Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser 195 200 205 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly 210 215 220 Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala 225 230 235 240 Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser 245 250 255 Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Tyr Gly Pro Gly Gln 260 265 270 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser 275 280 285 Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Pro Ser Ala Ala Ala 290 295 300 Ala Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala 305 310 315 320 Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Gln Gln 325 330 335 Gly Pro Gly Gln Tyr Gly Pro Gly Ser Ser Gly Pro Gly Gln Gln Gly 340 345 350 Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser 355 360 365 Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Pro Ser Ala Ala 370 375 380 Ala Ala Ala Ala Ala Gly Ser Tyr Gln Gln Gly Pro Gly Gln Gln Gly 385 390 395 400 Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly 405 410 415 Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr 420 425 430 Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala 435 440 445 Ala Gly Ser Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro 450 455 460 Gly Gln Ser Gly Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly 465 470 475 480 Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro 485 490 495 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala 500 505 510 Ala Ala Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln 515 520 525 Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly 530 535 540 Pro Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln 545 550 555 560 Gly Pro Gly Ala Ser 565 <210> 9 <211> 2364 <212> PRT <213> Artificial Sequence <220> <223> Met-PRT799 <400> 9 Met Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Gly Gln Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly 20 25 30 Gln Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly 35 40 45 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro 50 55 60 Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 65 70 75 80 Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly Gln Tyr Gly Pro Gly Gln 85 90 95 Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 100 105 110 Gly Gln Tyr Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Ser Ala 115 120 125 Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr 130 135 140 Gly Pro Gly Ala Ser Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly 145 150 155 160 Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro 165 170 175 Gly Gln Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr 180 185 190 Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly 195 200 205 Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala 210 215 220 Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser 225 230 235 240 Ala Ala Ala Ala Ala Gly Gln Tyr Gly Tyr Gly Pro Gly Gln Gln Gly 245 250 255 Pro Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln 260 265 270 Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala 275 280 285 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 290 295 300 Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Tyr Gly 305 310 315 320 Pro Gly Ser Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser 325 330 335 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 340 345 350 Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln 355 360 365 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly 370 375 380 Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 385 390 395 400 Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala 405 410 415 Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr 420 425 430 Gly Pro Gly Gln Ser Gly Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro 435 440 445 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro 450 455 460 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala 465 470 475 480 Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly 485 490 495 Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser 500 505 510 Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly 515 520 525 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly 530 535 540 Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser 545 550 555 560 Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala 565 570 575 Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly Gln 580 585 590 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln 595 600 605 Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Ser Gly Gln Tyr 610 615 620 Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala 625 630 635 640 Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 645 650 655 Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly 660 665 670 Pro Gly Ala Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln 675 680 685 Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser 690 695 700 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly 705 710 715 720 Pro Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser 725 730 735 Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala 740 745 750 Ala Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro 755 760 765 Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly 770 775 780 Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Gln Gln Gly 785 790 795 800 Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro 805 810 815 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 820 825 830 Gly Gln Tyr Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly 835 840 845 Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln 850 855 860 Gln Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln 865 870 875 880 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr 885 890 895 Gly Pro Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro Gly Ser Ser Gly 900 905 910 Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala 915 920 925 Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln 930 935 940 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln 945 950 955 960 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Gln Gly Pro Tyr 965 970 975 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly 980 985 990 Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Gln 995 1000 1005 Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro Gly Gln 1010 1015 1020 Ser Gly Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly Pro 1025 1030 1035 Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln 1040 1045 1050 Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly 1055 1060 1065 Pro Gly Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly 1070 1075 1080 Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln 1085 1090 1095 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln 1100 1105 1110 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 1115 1120 1125 Gln Tyr Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly 1130 1135 1140 Gln Ser Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr 1145 1150 1155 Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly 1160 1165 1170 Pro Gly Ala Ser Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser 1175 1180 1185 Ala Ala Ala Ala Ala Gly Gln Asn Gly Pro Gly Ser Gly Gln Gln 1190 1195 1200 Gly Pro Gly Gln Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 1205 1210 1215 Gly Gln Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro 1220 1225 1230 Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala 1235 1240 1245 Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser 1250 1255 1260 Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro 1265 1270 1275 Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro 1280 1285 1290 Gly Gln Gln Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly Pro 1295 1300 1305 Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser 1310 1315 1320 Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser 1325 1330 1335 Ala Ala Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly Gln Tyr 1340 1345 1350 Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser 1355 1360 1365 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser 1370 1375 1380 Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala 1385 1390 1395 Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser 1400 1405 1410 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Tyr Gly Pro Gly Gln 1415 1420 1425 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly 1430 1435 1440 Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala 1445 1450 1455 Ala Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly 1460 1465 1470 Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln 1475 1480 1485 Gly Pro Gly Gln Tyr Gly Pro Gly Ser Ser Gly Pro Gly Gln Gln 1490 1495 1500 Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln 1505 1510 1515 Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala 1520 1525 1530 Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly 1535 1540 1545 Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Gln Gly Pro Tyr 1550 1555 1560 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr 1565 1570 1575 Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala 1580 1585 1590 Gly Gln Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro 1595 1600 1605 Gly Gln Ser Gly Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro Tyr 1610 1615 1620 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro 1625 1630 1635 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala 1640 1645 1650 Ala Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln 1655 1660 1665 Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 1670 1675 1680 Gly Gln Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro 1685 1690 1695 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala 1700 1705 1710 Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly 1715 1720 1725 Pro Gly Gln Ser Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly 1730 1735 1740 Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln 1745 1750 1755 Gln Gly Pro Gly Ala Ser Gly Gln Gln Gly Pro Tyr Gly Pro Gly 1760 1765 1770 Ala Ser Ala Ala Ala Ala Ala Gly Gln Asn Gly Pro Gly Ser Gly 1775 1780 1785 Gln Gln Gly Pro Gly Gln Ser Gly Gln Tyr Gly Pro Gly Gln Gln 1790 1795 1800 Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 1805 1810 1815 Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser 1820 1825 1830 Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly 1835 1840 1845 Ala Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln 1850 1855 1860 Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser 1865 1870 1875 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala 1880 1885 1890 Gly Pro Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly 1895 1900 1905 Ala Ser Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser 1910 1915 1920 Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly 1925 1930 1935 Gln Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr 1940 1945 1950 Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser 1955 1960 1965 Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser 1970 1975 1980 Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro 1985 1990 1995 Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Tyr Gly Pro 2000 2005 2010 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly 2015 2020 2025 Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln 2030 2035 2040 Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly 2045 2050 2055 Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly 2060 2065 2070 Gln Gln Gly Pro Gly Gln Tyr Gly Pro Gly Ser Ser Gly Pro Gly 2075 2080 2085 Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 2090 2095 2100 Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln 2105 2110 2115 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln 2120 2125 2130 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Gln Gly 2135 2140 2145 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 2150 2155 2160 Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala 2165 2170 2175 Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr 2180 2185 2190 Gly Pro Gly Gln Ser Gly Pro Gly Ser Gly Gln Gln Gly Gln Gly 2195 2200 2205 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr 2210 2215 2220 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala 2225 2230 2235 Ala Ala Ala Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Ala Ser 2240 2245 2250 Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln 2255 2260 2265 Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln 2270 2275 2280 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 2285 2290 2295 Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln Gln Gly Pro 2300 2305 2310 Tyr Gly Pro Gly Gln Ser Gly Ser Gly Gln Gln Gly Pro Gly Gln 2315 2320 2325 Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser 2330 2335 2340 Gly Gln Gln Gly Ser Ser Val Asp Lys Leu Ala Ala Ala Leu Glu 2345 2350 2355 His His His His His His 2360 <210> 10 <211> 597 <212> PRT <213> Artificial Sequence <220> <223> Met-PRT313 <400> 10 Met Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Gly Gly Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly 20 25 30 Gly Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Gly Gln Gly 35 40 45 Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro 50 55 60 Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro Ser Ala Ser Ala Ala Ala 65 70 75 80 Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser Ala Ala 85 90 95 Ala Ala Ala Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro Gly Gln Gln 100 105 110 Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Ser Gly 115 120 125 Pro Gly Gln Gln Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly Pro 130 135 140 Gly Ser Gly Gly Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala 145 150 155 160 Ala Ala Ala Ala Gly Pro Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro 165 170 175 Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly 180 185 190 Gly Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly 195 200 205 Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gly Ser Ala Ala 210 215 220 Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr 225 230 235 240 Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Gly Gln Gly Pro Tyr Gly 245 250 255 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Tyr Gly Pro 260 265 270 Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala 275 280 285 Gly Gly Asn Gly Pro Gly Ser Gly Gly Tyr Gly Pro Gly Gln Gln Gly 290 295 300 Pro Gly Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Gly Gln Gly Pro 305 310 315 320 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro 325 330 335 Gly Gly Gln Gly Pro Gly Gly Tyr Gly Pro Gly Ser Ser Ala Ala Ala 340 345 350 Ala Ala Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala 355 360 365 Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly 370 375 380 Pro Gly Gly Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gln Gln Gly Pro 385 390 395 400 Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala 405 410 415 Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 420 425 430 Ala Ala Gly Pro Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro Ser Ala 435 440 445 Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Ser Gly Pro Gly Gly Tyr 450 455 460 Gly Pro Tyr Gly Pro Gly Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly 465 470 475 480 Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 485 490 495 Ala Ala Ala Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro 500 505 510 Gly Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gly Tyr Gly 515 520 525 Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gly Asn Gly Pro Gly Ser 530 535 540 Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly Ser Ala Ala Ala 545 550 555 560 Ala Ala Gly Gly Tyr Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly 565 570 575 Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln 580 585 590 Gly Pro Gly Ala Ser 595 <210> 11 <211> 12 <212> PRT <213> Synthetic sequence <220> <223> His tag <400> 11 Met His His His His His His Ser Ser Gly Ser Ser 1 5 10 <210> 12 <211> 608 <212> PRT <213> Synthetic sequence <220> <223> PRT380 <400> 12 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Gln 1 5 10 15 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln 20 25 30 Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Ser Ala Ala Ala 35 40 45 Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly 50 55 60 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro 65 70 75 80 Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 85 90 95 Ser Gly Gln Gln Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln 100 105 110 Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser 115 120 125 Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln Gln Gly 130 135 140 Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Tyr 145 150 155 160 Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 165 170 175 Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala 180 185 190 Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro Tyr 195 200 205 Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln 210 215 220 Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Ser 225 230 235 240 Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala 245 250 255 Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala 260 265 270 Ala Ala Ala Ala Gly Gln Tyr Gly Tyr Gly Pro Gly Gln Gln Gly Pro 275 280 285 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Asn Gly Pro 290 295 300 Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala 305 310 315 320 Ala Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala 325 330 335 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 340 345 350 Gly Gln Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly 355 360 365 Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly 370 375 380 Gln Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala 385 390 395 400 Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly Pro 405 410 415 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln 420 425 430 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 435 440 445 Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala 450 455 460 Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro 465 470 475 480 Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly 485 490 495 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln 500 505 510 Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala 515 520 525 Ala Ala Ala Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Ala Ser Ala 530 535 540 Ala Ala Ala Ala Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro 545 550 555 560 Gly Gln Gln Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Gln Tyr 565 570 575 Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala 580 585 590 Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser 595 600 605 <210> 13 <211> 601 <212> PRT <213> Artificial Sequence <220> <223> PRT410 <400> 13 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Gln 1 5 10 15 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln 20 25 30 Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Ser Gly Gln Tyr 35 40 45 Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala 50 55 60 Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 65 70 75 80 Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly 85 90 95 Pro Gly Ala Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln 100 105 110 Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser 115 120 125 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly 130 135 140 Pro Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser 145 150 155 160 Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala 165 170 175 Ala Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro 180 185 190 Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly 195 200 205 Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Gln Gln Gly 210 215 220 Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro 225 230 235 240 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 245 250 255 Gly Gln Tyr Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly 260 265 270 Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln 275 280 285 Gln Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln 290 295 300 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr 305 310 315 320 Gly Pro Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro Gly Ser Ser Gly 325 330 335 Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala 340 345 350 Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln 355 360 365 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln 370 375 380 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Gln Gly Pro Tyr 385 390 395 400 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly 405 410 415 Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Gln 420 425 430 Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro Gly Gln Ser 435 440 445 Gly Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly Pro Gly Ala 450 455 460 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 465 470 475 480 Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 485 490 495 Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln 500 505 510 Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala 515 520 525 Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly 530 535 540 Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln 545 550 555 560 Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Gln Gln Gly Pro 565 570 575 Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 580 585 590 Ser Gly Gln Gln Gly Pro Gly Ala Ser 595 600 <210> 14 <211> 576 <212> PRT <213> Artificial sequence <220> <223> PRT525 <400> 14 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Gln 1 5 10 15 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala 20 25 30 Gly Ser Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Ser Gly 35 40 45 Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser 50 55 60 Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly 65 70 75 80 Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro 85 90 95 Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly Gln Tyr Gly Pro Gly 100 105 110 Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala 115 120 125 Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr 130 135 140 Gly Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Tyr 145 150 155 160 Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Tyr Gly 165 170 175 Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala 180 185 190 Gly Ser Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro Tyr Ala Ser Ala 195 200 205 Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly Gln Gln 210 215 220 Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Gln Gln Gly Pro Gly 225 230 235 240 Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro 245 250 255 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 260 265 270 Ala Ala Gly Ser Tyr Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly 275 280 285 Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro 290 295 300 Gly Gln Gln Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Gly 305 310 315 320 Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala 325 330 335 Ala Ala Ala Gly Ser Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Tyr 340 345 350 Gly Pro Gly Ser Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly 355 360 365 Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Gln 370 375 380 Gln Gly Pro Tyr Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala 385 390 395 400 Gly Ser Tyr Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly 405 410 415 Ala Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala 420 425 430 Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln 435 440 445 Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly 450 455 460 Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro Gly Gln Ser Gly Pro 465 470 475 480 Gly Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala 485 490 495 Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Gln Gln Gly Pro 500 505 510 Tyr Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly 515 520 525 Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser 530 535 540 Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Pro Ser Ala Ala Ala 545 550 555 560 Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser 565 570 575 <210> 15 <211> 2375 <212> PRT <213> Artificial Sequence <220> <223> PRT799 <400> 15 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Gln 1 5 10 15 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln 20 25 30 Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Ser Gly Gln Tyr 35 40 45 Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala 50 55 60 Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 65 70 75 80 Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly 85 90 95 Pro Gly Ala Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln 100 105 110 Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser 115 120 125 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly 130 135 140 Pro Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser 145 150 155 160 Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala 165 170 175 Ala Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro 180 185 190 Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly 195 200 205 Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Gln Gln Gly 210 215 220 Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro 225 230 235 240 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 245 250 255 Gly Gln Tyr Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly 260 265 270 Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln 275 280 285 Gln Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln 290 295 300 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr 305 310 315 320 Gly Pro Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro Gly Ser Ser Gly 325 330 335 Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala 340 345 350 Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln 355 360 365 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln 370 375 380 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Gln Gly Pro Tyr 385 390 395 400 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly 405 410 415 Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Gln 420 425 430 Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro Gly Gln Ser 435 440 445 Gly Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly Pro Gly Ala 450 455 460 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 465 470 475 480 Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 485 490 495 Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln 500 505 510 Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala 515 520 525 Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly 530 535 540 Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln 545 550 555 560 Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Gln Gln Gly Pro 565 570 575 Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 580 585 590 Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly Gln Gln Gly Pro Tyr Gly 595 600 605 Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Asn Gly Pro Gly Ser 610 615 620 Gly Gln Gln Gly Pro Gly Gln Ser Gly Gln Tyr Gly Pro Gly Gln Gln 625 630 635 640 Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly 645 650 655 Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala 660 665 670 Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly 675 680 685 Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser 690 695 700 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln Gln 705 710 715 720 Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln 725 730 735 Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Tyr 740 745 750 Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly 755 760 765 Ser Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro Tyr Ala Ser Ala Ala 770 775 780 Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr 785 790 795 800 Gly Pro Gly Gln Ser Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly 805 810 815 Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro 820 825 830 Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Tyr 835 840 845 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Gln Asn 850 855 860 Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln 865 870 875 880 Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro 885 890 895 Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln 900 905 910 Gly Pro Gly Gln Tyr Gly Pro Gly Ser Ser Gly Pro Gly Gln Gln Gly 915 920 925 Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly 930 935 940 Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala 945 950 955 960 Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro 965 970 975 Gly Ala Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser 980 985 990 Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly 995 1000 1005 Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly 1010 1015 1020 Pro Gly Gln Tyr Gly Pro Tyr Gly Pro Gly Gln Ser Gly Pro Gly 1025 1030 1035 Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala 1040 1045 1050 Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Tyr 1055 1060 1065 Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 1070 1075 1080 Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly 1085 1090 1095 Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala Ala Ala 1100 1105 1110 Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr 1115 1120 1125 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser 1130 1135 1140 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser 1145 1150 1155 Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala 1160 1165 1170 Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser 1175 1180 1185 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala 1190 1195 1200 Ala Gly Gln Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln 1205 1210 1215 Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly 1220 1225 1230 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly 1235 1240 1245 Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly 1250 1255 1260 Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly Gln Tyr Gly 1265 1270 1275 Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala 1280 1285 1290 Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln Gln Gly 1295 1300 1305 Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln 1310 1315 1320 Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln 1325 1330 1335 Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala 1340 1345 1350 Ala Gly Ser Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro Tyr Ala 1355 1360 1365 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln 1370 1375 1380 Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Gln Gln Gly 1385 1390 1395 Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly 1400 1405 1410 Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala 1415 1420 1425 Ala Ala Gly Gln Tyr Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr 1430 1435 1440 Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr 1445 1450 1455 Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala 1460 1465 1470 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1475 1480 1485 Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln 1490 1495 1500 Tyr Gly Pro Gly Ser Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly 1505 1510 1515 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly 1520 1525 1530 Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala 1535 1540 1545 Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro 1550 1555 1560 Gly Ala Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala 1565 1570 1575 Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly Gln 1580 1585 1590 Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly 1595 1600 1605 Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro Gly Gln Ser Gly 1610 1615 1620 Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly Pro Gly Ala 1625 1630 1635 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly 1640 1645 1650 Pro Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly 1655 1660 1665 Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly 1670 1675 1680 Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala 1685 1690 1695 Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly 1700 1705 1710 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr 1715 1720 1725 Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser 1730 1735 1740 Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser 1745 1750 1755 Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly 1760 1765 1770 Ala Ser Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1775 1780 1785 Ala Ala Ala Gly Gln Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro 1790 1795 1800 Gly Gln Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln 1805 1810 1815 Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln 1820 1825 1830 Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala 1835 1840 1845 Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly Gln 1850 1855 1860 Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser 1865 1870 1875 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln 1880 1885 1890 Gln Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser 1895 1900 1905 Gly Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro 1910 1915 1920 Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala 1925 1930 1935 Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro 1940 1945 1950 Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro 1955 1960 1965 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Gln 1970 1975 1980 Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala 1985 1990 1995 Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala 2000 2005 2010 Ala Ala Ala Ala Gly Gln Tyr Gly Tyr Gly Pro Gly Gln Gln Gly 2015 2020 2025 Pro Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly 2030 2035 2040 Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala Ala Ala 2045 2050 2055 Ala Ala Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser 2060 2065 2070 Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 2075 2080 2085 Gly Gln Tyr Gly Pro Gly Ser Ser Gly Pro Gly Gln Gln Gly Pro 2090 2095 2100 Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly 2105 2110 2115 Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala Ala 2120 2125 2130 Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr 2135 2140 2145 Gly Pro Gly Ala Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro 2150 2155 2160 Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro 2165 2170 2175 Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Gln 2180 2185 2190 Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro Gly Gln 2195 2200 2205 Ser Gly Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly Pro 2210 2215 2220 Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Gln 2225 2230 2235 Gln Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly 2240 2245 2250 Pro Gly Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly 2255 2260 2265 Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln 2270 2275 2280 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly Pro Gly Gln 2285 2290 2295 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 2300 2305 2310 Gln Tyr Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly 2315 2320 2325 Gln Ser Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr 2330 2335 2340 Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly 2345 2350 2355 Ser Ser Val Asp Lys Leu Ala Ala Ala Leu Glu His His His His 2360 2365 2370 His His 2375 <210> 16 <211> 608 <212> PRT <213> Artificial Sequence <220> <223> PRT313 <400> 16 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Gly 1 5 10 15 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gly 20 25 30 Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gly Ser Ala Ala Ala 35 40 45 Ala Ala Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro Gly Gln Gln Gly 50 55 60 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Gly Tyr Gly Pro 65 70 75 80 Gly Gly Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 85 90 95 Ser Gly Gln Gln Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gly 100 105 110 Tyr Gly Pro Gly Gly Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser 115 120 125 Ala Ala Ala Ala Ala Gly Gly Tyr Gly Ser Gly Pro Gly Gln Gln Gly 130 135 140 Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gly Tyr 145 150 155 160 Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 165 170 175 Pro Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro Ser Ala Ser Ala Ala 180 185 190 Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly Gly Tyr Gly Pro Tyr 195 200 205 Ala Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Ser Gly Pro Gly Gln 210 215 220 Gln Gly Pro Tyr Gly Pro Gly Gly Ser Ala Ala Ala Ala Ala Gly Ser 225 230 235 240 Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala 245 250 255 Ala Ala Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala 260 265 270 Ala Ala Ala Ala Gly Gly Tyr Gly Tyr Gly Pro Gly Gly Gln Gly Pro 275 280 285 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gly Asn Gly Pro 290 295 300 Gly Ser Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly Ser Ala 305 310 315 320 Ala Ala Ala Ala Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala 325 330 335 Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro 340 345 350 Gly Gly Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly 355 360 365 Gly Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly 370 375 380 Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gly Ser Ala 385 390 395 400 Ala Ala Ala Ala Gly Gly Tyr Gln Gln Gly Pro Gly Gly Gln Gly Pro 405 410 415 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Gly Gln 420 425 430 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 435 440 445 Gly Tyr Gly Pro Gly Gly Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala 450 455 460 Ala Gly Gly Tyr Gly Ser Gly Pro Gly Gly Tyr Gly Pro Tyr Gly Pro 465 470 475 480 Gly Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly 485 490 495 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gly 500 505 510 Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gly Ser Ala Ala 515 520 525 Ala Ala Ala Gly Pro Gly Ser Gly Gly Tyr Gly Pro Gly Ala Ser Ala 530 535 540 Ala Ala Ala Ala Gly Gly Asn Gly Pro Gly Ser Gly Gly Tyr Gly Pro 545 550 555 560 Gly Gln Gln Gly Pro Gly Gly Ser Ala Ala Ala Ala Ala Gly Gly Tyr 565 570 575 Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala 580 585 590 Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser 595 600 605 <210> 17 <211> 590 <212> PRT <213> Artificial Sequence <220> <223> Met-PRT399​​​Met Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Gly Gly Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly 20 25 30 Gly Ser Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro Gly Gln Gln Gly 35 40 45 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Gly Tyr Gly Pro 50 55 60 Gly Gly Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 65 70 75 80 Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly Gly Tyr Gly Pro Gly Gly 85 90 95 Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 100 105 110 Gly Gly Tyr Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Ser Ala 115 120 125 Ala Ala Ala Ala Gly Pro Gly Ser Gly Gly Tyr Gly Gln Gly Pro Tyr 130 135 140 Gly Pro Gly Ala Ser Gly Pro Gly Gly Tyr Gly Pro Gly Gly Gln Gly 145 150 155 160 Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro 165 170 175 Gly Gly Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gly Tyr 180 185 190 Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gly Ser Gly 195 200 205 Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala 210 215 220 Ala Ala Ala Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ser Ser 225 230 235 240 Ala Ala Ala Ala Ala Gly Gly Tyr Gly Tyr Gly Pro Gly Gly Gln Gly 245 250 255 Pro Tyr Gly Pro Gly Ala Ser Gly Gly Asn Gly Pro Gly Ser Gly Gly 260 265 270 Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly Ser Ala Ala Ala Ala Ala 275 280 285 Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 290 295 300 Ala Ala Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro Gly Gly Tyr Gly 305 310 315 320 Pro Gly Ser Ser Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ser 325 330 335 Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro 340 345 350 Tyr Gly Pro Gly Gly Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gln Gln 355 360 365 Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly 370 375 380 Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 385 390 395 400 Pro Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro Ser Ala Ser Ala Ala 405 410 415 Ala Ala Ala Gly Gly Tyr Gly Ser Gly Pro Gly Gly Tyr Gly Pro Tyr 420 425 430 Gly Pro Gly Gly Ser Gly Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro 435 440 445 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro 450 455 460 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gly Ser Ala Ala Ala Ala Ala 465 470 475 480 Gly Pro Gly Ser Gly Gly Tyr Gly Pro Gly Ala Ser Gly Gly Asn Gly 485 490 495 Pro Gly Ser Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly Ser 500 505 510 Ala Ala Ala Ala Ala Gly Gly Tyr Gln Gln Gly Pro Gly Gly Gln Gly 515 520 525 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly 530 535 540 Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gly Ser Gly Ser 545 550​​​​​​​​​​​​​​​​​​​​​​​​​​​Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gly 20 25 30 Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gly Ser Gly Gly Tyr 35 40 45 Gly Pro Gly Gly Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala 50 55 60 Ala Ala Ala Ala Gly Pro Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro 65 70 75 80 Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly 85 90 95 Pro Gly Ala Ser Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro Gly Gln 100 105 110 Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Ser 115 120 125 Gly Pro Gly Gln Gln Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly 130 135 140 Pro Gly Ser Gly Gly Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser 145 150 155 160 Gly Pro Gly Gly Tyr Gly Pro Gly Gly Gln Gly Pro Ser Ala Ser Ala 165 170 175 Ala Ala Ala Ala Gly Ser Gly Gln Gln Gly Pro Gly Gly Tyr Gly Pro 180 185 190 Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Ser Gly Pro Gly 195 200 205 Gln Gln Gly Pro Tyr Gly Pro Gly Gly Ser Gly Ser Gly Gln Gln Gly 210 215 220 Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro 225 230 235 240 Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 245 250 255 Gly Gly Tyr Gly Tyr Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly 260 265 270 Ala Ser Gly Gly Asn Gly Pro Gly Ser Gly Gly Tyr Gly Pro Gly Gln 275 280 285 Gln Gly Pro Gly Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Gly Gln 290 295 300 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gly Tyr 305 310 315 320 Gly Pro Gly Gly Gln Gly Pro Gly Gly Tyr Gly Pro Gly Ser Ser Gly 325 330 335 Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala 340 345 350 Ala Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gly 355 360 365 Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gln Gln Gly Pro Gly Gly Gln 370 375 380 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gly Gln Gly Pro Tyr 385 390 395 400 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Gly Tyr Gly 405 410 415 Pro Gly Gly Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Gly 420 425 430 Tyr Gly Ser Gly Pro Gly Gly Tyr Gly Pro Tyr Gly Pro Gly Gly Ser 435 440 445 Gly Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly Pro Gly Ala 450 455 460 Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro 465 470 475 480 Tyr Gly Pro Gly Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 485 490 495 Gly Tyr Gly Pro Gly Ala Ser Gly Gly Asn Gly Pro Gly Ser Gly Gly 500 505 510 Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly Ser Ala Ala Ala Ala Ala 515 520 525 Gly Gly Tyr Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly 530 535 540 Ala Ser Ala Ala Ala Ala Ala Gly Gly Tyr Gly Ser Gly Pro Gly Gln 545 550 555 560 Gln Gly Pro Tyr Gly Pro Gly Gly Ser Gly Ser Gly Gln Gln Gly Pro 565 570 575 Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 580 585 590 Ser Gly Gln Gln Gly Pro Gly Ala Ser 595 600 <210> 19 <211> 见序列612 <212> 蛋白质 <213> 人工序列 <220> <223> Met - PRT720 <400> 19 Met Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Gly Gln Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly 20 25 30 Gln Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly 35 40 45 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Val Leu 50 55 60 Ile Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Ser Ala Ser Ala Ala 65 70 75 80 Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly 85 90 95 Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser 100 105 110 Ser Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser Val Leu Ile Gly Pro 115 120 125 Gly Gln Gln Val Leu Ile Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala 130 135 140 Gly Pro Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala 145 150 155 160 Ser Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser 165 170 175 Ala Ala Ala Ala Ala Gly Ser Gly Gln Gln Val Leu Ile Gly Pro Gly 180 185 190 Gln Tyr Val Leu Ile Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly 195 200 205 Gln Tyr Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln 210 215 220 Ser Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser 225 230 235 240 Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr 245 250 255 Val Leu Ile Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr 260 265 270 Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly 275 280 285 Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro 290 295 300 Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln Val Leu Ile 305 310 315 320 Gly Pro Tyr Val Leu Ile Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala 325 330 335 Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro Gly 340 345 350 Ser Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala 355 360 365 Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Gln Gln Val Leu Ile Gly 370 375 380 Pro Tyr Val Leu Ile Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Gly 385 390 395 400 Gln Tyr Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala 405 410 415 Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 420 425 430 Ala Ala Ala Gly Pro Gly Gln Tyr Val Leu Ile Gly Pro Gly Gln Gln 435 440 445 Val Leu Ile Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr 450 455 460 Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro Gly Gln Ser Gly 465 470 475 480 Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser 485 490 495 Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Gln Gln Val Leu Ile 500 505 510 Gly Pro Tyr Val Leu Ile Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala 515 520 525 Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly 530 535 540 Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser 545 550 555 560 Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln Val Leu Ile Gly Pro Gly 565 570 575 Gln Gln Gly Pro Tyr Val Leu Ile Gly Pro Gly Ala Ser Ala Ala Ala 580 585 590 Ala Ala Gly Pro Gly Ser Gly Gln Gln Val Leu Ile Gly Pro Gly Ala 595 600 605 Ser Val Leu Ile 610 <210> 20 <211> 592 <212> PRT <213> Synthetic sequence <220> <223> Met-PRT665 <400> 20 Met Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Gly Ser Asn Gly Pro Gly Ser Gly Gln Gln Gly 20 25 30 Pro Gly Gln Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln 35 40 45 Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly 50 55 60 Gln Tyr Val Leu Ile Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala 65 70 75 80 Ala Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly 85 90 95 Ala Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly 100 105 110 Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser 115 120 125 Val Leu Ile Gly Pro Gly Gln Gln Gly Pro Tyr Gly Ser Ala Ala Ala 130 135 140 Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr 145 150 155 160 Gly Pro Gly Ala Ser Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly 165 170 175 Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Gln Gln 180 185 190 Val Leu Ile Gly Pro Gly Gln Tyr Gly Pro Tyr Ala Ser Ala Ala Ala 195 200 205 Ala Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly Gln Gln Gly Pro 210 215 220 Tyr Gly Pro Gly Gln Ser Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln 225 230 235 240 Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln 245 250 255 Gln Val Leu Ile Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala 260 265 270 Ala Ala Ala Gly Ser Tyr Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr 275 280 285 Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly 290 295 300 Pro Gly Gln Gln Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala 305 310 315 320 Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr Gly Pro Gly Ala Ser 325 330 335 Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Gln Gln Gly 340 345 350 Pro Gly Gln Tyr Gly Pro Gly Ser Ser Gly Pro Gly Gln Gln Gly Pro 355 360 365 Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr 370 375 380 Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr Gly Pro Gly Pro Ser 385 390 395 400 Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gln Gln Gly Pro Gly Gln 405 410 415 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Gln Gly Pro 420 425 430 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly 435 440 445 Gln Tyr Val Leu Ile Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala 450 455 460 Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly Gln Tyr 465 470 475 480 Gly Pro Tyr Gly Pro Gly Gln Ser Gly Pro Gly Ser Gly Gln Gln Gly 485 490 495 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala 500 505 510 Gly Ser Tyr Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr Gly Pro 515 520 525 Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln 530 535 540 Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr 545 550 555 560 Gly Pro Gly Gln Gln Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala 565 570 575 Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser Val Leu Ile 580 585 590 <210> 21 <211> 619 <212> PRT <213> Artificial Sequence <220> <223> Met-PRT666 <400> 21 Met Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Gly Ser Asn Gly Pro Gly Ser Gly Gln Gln Gly 20 25 30 Pro Gly Gln Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln 35 40 45 Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly 50 55 60 Gln Tyr Val Leu Ile Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Ser 65 70 75 80 Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln 85 90 95 Gly Pro Gly Ala Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly 100 105 110 Gln Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser 115 120 125 Tyr Gly Ser Val Leu Ile Gly Pro Gly Gln Gln Val Leu Ile Gly Pro 130 135 140 Tyr Gly Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln 145 150 155 160 Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Tyr 165 170 175 Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala 180 185 190 Ala Gly Ser Gly Gln Gln Val Leu Ile Gly Pro Gly Gln Tyr Val Leu 195 200 205 Ile Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr 210 215 220 Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly 225 230 235 240 Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala 245 250 255 Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr 260 265 270 Val Leu Ile Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly 275 280 285 Ser Tyr Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala 290 295 300 Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln 305 310 315 320 Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln 325 330 335 Gln Val Leu Ile Gly Pro Tyr Val Leu Ile Gly Pro Gly Ala Ser Ala 340 345 350 Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Gln Gln Gly Pro 355 360 365 Gly Gln Tyr Gly Pro Gly Ser Ser Gly Pro Gly Gln Gln Gly Pro Tyr 370 375 380 Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly 385 390 395 400 Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr Val Leu Ile Gly Pro Gly 405 410 415 Pro Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gln Gln Gly Pro 420 425 430 Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Gln 435 440 445 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly 450 455 460 Pro Gly Gln Tyr Val Leu Ile Gly Pro Gly Gln Gln Val Leu Ile Gly 465 470 475 480 Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser 485 490 495 Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro Gly Gln Ser Gly Pro Gly 500 505 510 Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 515 520 525 Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Gln Gln Val Leu Ile 530 535 540 Gly Pro Tyr Val Leu Ile Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala 545 550 555 560 Ala Ala Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln 565 570 575 Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly 580 585 590 Pro Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln 595 600 605 Val Leu Ile Gly Pro Gly Ala Ser Val Leu Ile 610 615 <210> 22 <211> 623 <212> PRT <213> Artificial Sequence <220> <223> PRT720 <400> 22 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Gln 1 5 10 15 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln 20 25 30 Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Ser Gly Gln Tyr 35 40 45 Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala 50 55 60 Ala Ala Ala Ala Gly Pro Gly Gln Tyr Val Leu Ile Gly Pro Gly Gln 65 70 75 80 Gln Val Leu Ile Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro 85 90 95 Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly Gln Tyr Gly Pro Gly 100 105 110 Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala Ala Ala Ala 115 120 125 Ala Gly Ser Tyr Gly Ser Val Leu Ile Gly Pro Gly Gln Gln Val Leu 130 135 140 Ile Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 145 150 155 160 Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln 165 170 175 Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala 180 185 190 Gly Ser Gly Gln Gln Val Leu Ile Gly Pro Gly Gln Tyr Val Leu Ile 195 200 205 Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly 210 215 220 Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Gln 225 230 235 240 Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala 245 250 255 Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr Val Leu Ile Gly Pro 260 265 270 Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Tyr Gly Pro Gly 275 280 285 Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly 290 295 300 Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala Ala 305 310 315 320 Ala Ala Ala Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr Val Leu 325 330 335 Ile Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro 340 345 350 Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro Gly Ser Ser Gly Pro Gly 355 360 365 Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly 370 375 380 Ser Tyr Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr Val Leu Ile 385 390 395 400 Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gln Gln Gly 405 410 415 Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln 420 425 430 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro 435 440 445 Gly Gln Tyr Val Leu Ile Gly Pro Gly Gln Gln Val Leu Ile Gly Pro 450 455 460 Ser Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly 465 470 475 480 Gln Tyr Gly Pro Tyr Gly Pro Gly Gln Ser Gly Pro Gly Ser Gly Gln 485 490 495 Gln Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala 500 505 510 Gly Ser Tyr Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr Val Leu 515 520 525 Ile Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 530 535 540 Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln 545 550 555 560 Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala 565 570 575 Gly Gln Tyr Gln Gln Val Leu Ile Gly Pro Gly Gln Gln Gly Pro Tyr 580 585 590 Val Leu Ile Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 595 600 605 Ser Gly Gln Gln Val Leu Ile Gly Pro Gly Ala Ser Val Leu Ile 610 615 620 <210> 23 <211> 603 <212> PRT <213> Artificial Sequence <220> <223> PRT665 <400> 23 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Gln 1 5 10 15 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala 20 25 30 Gly Ser Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Ser Gly 35 40 45 Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser 50 55 60 Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Val Leu Ile 65 70 75 80 Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala 85 90 95 Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser Gly Gln Tyr 100 105 110 Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser Ser Ala 115 120 125 Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser Val Leu Ile Gly Pro 130 135 140 Gly Gln Gln Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Ala Ala Gly 145 150 155 160 Pro Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser 165 170 175 Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala 180 185 190 Ala Ala Ala Ala Ala Ala Gly Ser Gly Gln Gln Val Leu Ile Gly Pro 195 200 205 Gly Gln Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly 210 215 220 Ser Tyr Gly Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Gln 225 230 235 240 Ser Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Ala Ser 245 250 255 Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln Val Leu Ile Gly 260 265 270 Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser 275 280 285 Tyr Gly Tyr Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser 290 295 300 Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly 305 310 315 320 Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln 325 330 335 Val Leu Ile Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala 340 345 350 Ala Ala Gly Ser Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Tyr Gly 355 360 365 Pro Gly Ser Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser 370 375 380 Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Gln Gln 385 390 395 400 Val Leu Ile Gly Pro Tyr Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala 405 410 415 Ala Ala Gly Ser Tyr Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly 420 425 430 Pro Gly Ala Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala 435 440 445 Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Val Leu Ile 450 455 460 Gly Pro Gly Gln Gln Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala 465 470 475 480 Ala Gly Ser Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro 485 490 495 Gly Gln Ser Gly Pro Gly Ser Gly Gln Gln Gly Gln Gly Pro Tyr Gly 500 505 510 Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro 515 520 525 Gly Gln Gln Val Leu Ile Gly Pro Tyr Gly Pro Gly Pro Ser Ala Ala 530 535 540 [[ID=2​​​​​​​​​​​​​​​​​​​​​​​​ <223> PRT666 <400> 24 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Gln 1 5 10 15 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala 20 25 30 Gly Ser Asn Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Ser Gly 35 40 45 Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Ser 50 55 60 Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Val Leu Ile 65 70 75 80 Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Ser Ala Ser Ala Ala Ala 85 90 95 Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Ala Ser 100 105 110 Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly 115 120 125 Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser Val Leu 130 135 140 Ile Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr Gly Ser Ala Ala 145 150 155 160 Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Tyr Gly Gln Gly Pro 165 170 175 Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Tyr Gly Pro Gly Gln Gln 180 185 190 Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Gln 195 200 205 Gln Val Leu Ile Gly Pro Gly Gln Tyr Val Leu Ile Gly Pro Tyr Ala 210 215 220 Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly 225 230 235 240 Gln Gln Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Gln Gln Gly 245 250 255 Pro Gly Gln Gln Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Ala Ala 260 265 270 Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr Val Leu Ile Gly Pro 275 280 285 Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Tyr Gly 290 295 300 Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly 305 310 315 320 Pro Gly Ser Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Pro Ser 325 330 335 Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Gln Val Leu Ile Gly 340 345 350 Pro Tyr Val Leu Ile Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala 355 360 365 Ala Gly Ser Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gln Tyr Gly Pro 370 375 380 Gly Ser Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro Gly Ser Ser 385 390 395 400 Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Gln Gln Val 405 410 415 Leu Ile Gly Pro Tyr Val Leu Ile Gly Pro Gly Pro Ser Ala Ala Ala 420 425 430 Ala Ala Ala Ala Gly Ser Tyr Gln Gln Gly Pro Gly Gln Gln Gly Pro 435 440 445 Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Gln Gly Pro Tyr Gly Pro 450 455 460 Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Val 465 470 475 480 Leu Ile Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Ser Ala Ser Ala 485 490 495 Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly Gln Tyr 500 505 510 Gly Pro Tyr Gly Pro Gly Gln Ser Gly Pro Gly Ser Gly Gln Gln Gly 515 520 525 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala 530 535 540 Gly Ser Tyr Gly Pro Gly Gln Gln Val Leu Ile Gly Pro Tyr Val Leu 545 550 555 560 Ile Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly 565 570 575 Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser 580 585 590 Gly Gln Tyr Gly Pro Gly Gln Gln Gly Pro Gly Pro Ser Ala Ala Ala 595 600 605 Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Gln Val Leu Ile Gly Pro 610 615 620 Gly Ala Ser Val Leu Ile 625 630 <210> 25 <211> 593 <212> PRT <213> Artificial Sequence <220> <223> Met-PRT888 <400> 25 Met Gly Ser Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala 1 5 10 15 Ser Ala Ala Ala Ala Ala Gly Gln Asn Gly Pro Gly Ser Gly Val Leu 20 25 30 Gly Pro Gly Gln Ser Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro Gly 35 40 45 Val Leu Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln 50 55 60 Tyr Gly Pro Gly Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala 65 70 75 80 Gly Pro Gly Ser Gly Val Leu Gly Pro Gly Ala Ser Gly Gln Tyr Gly 85 90 95 Pro Gly Val Leu Gly Pro Gly Val Leu Gly Pro Gly Ser Ser Ala Ala 100 105 110 Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Val Leu Gly Pro Tyr 115 120 125 Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Tyr Gly Gln 130 135 140 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Tyr Gly Pro Gly 145 150 155 160 Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Val 165 170 175 Leu Gly Pro Gly Gln Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala 180 185 190 Gly Gln Tyr Gly Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly 195 200 205 Gln Ser Gly Ser Gly Val Leu Gly Pro Gly Val Leu Gly Pro Tyr Ala 210 215 220 Ser Ala Ala Ala Ala Ala Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro 225 230 235 240 Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Tyr Gly Pro Gly 245 250 255 Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly 260 265 270 Ser Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro Gly Gln Ser Ala Ala 275 280 285 Ala Ala Ala Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser 290 295 300 Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro Gly 305 310 315 320 Gln Tyr Gly Pro Gly Ser Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly 325 330 335 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Val 340 345 350 Leu Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Gln 355 360 365 Tyr Val Leu Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser 370 375 380 Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 385 390 395 400 Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro Ser Ala 405 410 415 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Gln Tyr 420 425 430 Gly Pro Tyr Gly Pro Gly Gln Ser Gly Pro Gly Ser Gly Val Leu Gly 435 440 445 Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln 450 455 460 Tyr Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Gln Ser Ala Ala 465 470 475 480 Ala Ala Ala Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly 485 490 495 Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro 500 505 510 Gly Gln Ser Ala Ala Ala Ala Ala Gly Gln Tyr Val Leu Gly Pro Gly 515 520 525 Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 530 535 540 Gln Tyr Gly Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Gln 545 550 555 560 Ser Gly Ser Gly Val Leu Gly Pro Gly Val Leu Gly Pro Tyr Ala Ser 565 570 575 Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Leu Gly Pro Gly Ala 580 585 590 Ser <210> 26 <211> 590 <212> PRT <213> Artificial sequence <220> <223> Met-PRT965 <400> 26 Met Gly Pro Gly Thr Ser Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Gly Ala Asn Gly Pro Gly Ser Gly Thr Ser Gly Pro Gly 20 25 30 Ala Ser Gly Ala Tyr Gly Pro Gly Thr Ser Gly Pro Gly Thr Ser Gly 35 40 45 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Ala Tyr Gly Pro 50 55 60 Gly Thr Ser Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 65 70 75 80 Ser Gly Thr Ser Gly Pro Gly Ala Ser Gly Ala Tyr Gly Pro Gly Thr 85 90 95 Ser Gly Pro Gly Thr Ser Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 100 105 110 Gly Ala Tyr Gly Ser Gly Pro Gly Thr Ser Gly Pro Tyr Gly Ser Ala 115 120 125 Ala Ala Ala Ala Gly Pro Gly Ser Gly Ala Tyr Gly Ala Gly Pro Tyr 130 135 140 Gly Pro Gly Ala Ser Gly Pro Gly Ala Tyr Gly Pro Gly Thr Ser Gly 145 150 155 160 Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Thr Ser Gly Pro 165 170 175 Gly Ala Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Ala Tyr 180 185 190 Gly Ser Gly Pro Gly Thr Ser Gly Pro Tyr Gly Pro Gly Ala Ser Gly 195 200 205 Ser Gly Thr Ser Gly Pro Gly Thr Ser Gly Pro Tyr Ala Ser Ala Ala 210 215 220 Ala Ala Ala Gly Pro Gly Thr Ser Gly Pro Tyr Gly Pro Gly Ser Ser 225 230 235 240 Ala Ala Ala Ala Ala Gly Ala Tyr Gly Tyr Gly Pro Gly Thr Ser Gly 245 250 255 Pro Tyr Gly Pro Gly Ala Ser Gly Ala Asn Gly Pro Gly Ser Gly Ala 260 265 270 Tyr Gly Pro Gly Thr Ser Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala 275 280 285 Gly Pro Gly Thr Ser Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 290 295 300 Ala Ala Gly Ala Tyr Gly Pro Gly Thr Ser Gly Pro Gly Ala Tyr Gly 305 310 315 320 Pro Gly Ser Ser Gly Pro Gly Thr Ser Gly Pro Tyr Gly Pro Gly Ser 325 330 335 Ser Ala Ala Ala Ala Ala Gly Ala Tyr Gly Pro Gly Thr Ser Gly Pro 340 345 350 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ala Tyr Thr Ser 355 360 365 Gly Pro Gly Thr Ser Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly 370 375 380 Thr Ser Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 385 390 395 400 Pro Gly Ala Tyr Gly Pro Gly Thr Ser Gly Pro Ser Ala Ser Ala Ala 405 410 415 Ala Ala Ala Gly Ala Tyr Gly Ser Gly Pro Gly Ala Tyr Gly Pro Tyr 420 425 430 Gly Pro Gly Ala Ser Gly Pro Gly Ser Gly Thr Ser Gly Ala Gly Pro 435 440 445 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ala Tyr Gly Pro 450 455 460 Gly Thr Ser Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala 465 470 475 480 Gly Pro Gly Ser Gly Ala Tyr Gly Pro Gly Ala Ser Gly Ala Asn Gly 485 490 495 Pro Gly Ser Gly Ala Tyr Gly Pro Gly Thr Ser Gly Pro Gly Ala Ser 500 505 510 Ala Ala Ala Ala Ala Gly Ala Tyr Thr Ser Gly Pro Gly Thr Ser Gly 515 520 525 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ala Tyr Gly 530 535 540 Ser Gly Pro Gly Thr Ser Gly Pro Tyr Gly Pro Gly Ala Ser Gly Ser[[ID=...]] 545 550 555 560 Gly Thr Ser Gly Pro Gly Thr Ser Gly Pro Tyr Ala Ser Ala Ala Ala 565 570 575 Ala Ala Gly Pro Gly Ser Gly Thr Ser Gly Pro Gly Ala Ser 580 585 590 <210> 27 <211> 593 <212> PRT <213> Artificial Sequence <220> <223> Met-PRT889 <400> 27 Met Gly Ser Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala 1 5 10 15 Ser Ala Ala Ala Ala Ala Gly Ile Asn Gly Pro Gly Ser Gly Val Leu 20 25 30 Gly Pro Gly Ile Ser Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro Gly 35 40 45 Val Leu Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Ile 50 55 60 Tyr Gly Pro Gly Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala 65 70 75 80 Gly Pro Gly Ser Gly Val Leu Gly Pro Gly Ala Ser Gly Ile Tyr Gly 85 90 95 Pro Gly Val Leu Gly Pro Gly Val Leu Gly Pro Gly Ser Ser Ala Ala 100 105 110 Ala Ala Ala Gly Ile Tyr Gly Ser Gly Pro Gly Val Leu Gly Pro Tyr 115 120 125 Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Ile Tyr Gly Ile 130 135 140 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Ile Tyr Gly Pro Gly 145 150 155 160 Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Val 165 170 175 Leu Gly Pro Gly Ile Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala 180 185 190 Gly Ile Tyr Gly Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly 195 200 205 Ile Ser Gly Ser Gly Val Leu Gly Pro Gly Val Leu Gly Pro Tyr Ala 210 215 220 Ser Ala Ala Ala Ala Ala Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro 225 230 235 240 Gly Ser Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Tyr Gly Pro Gly 245 250 255 Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser Gly Ile Asn Gly Pro Gly 260 265 270 Ser Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro Gly Ile Ser Ala Ala 275 280 285 Ala Ala Ala Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser 290 295 300 Ala Ala Ala Ala Ala Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro Gly 305 310 315 320 Ile Tyr Gly Pro Gly Ser Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly 325 330 335 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Pro Gly Val 340 345 350 Leu Gly Pro Tyr Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala Gly Ile 355 360 365 Tyr Val Leu Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser 370 375 380 Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 385 390 395 400 Ala Ala Gly Pro Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro Ser Ala 405 410 415 Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser Gly Pro Gly Ile Tyr 420 425 430 Gly Pro Tyr Gly Pro Gly Ile Ser Gly Pro Gly Ser Gly Val Leu Gly 435 440 445 Ile Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile 450 455 460 Tyr Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ile Ser Ala Ala 465 470 475 480 Ala Ala Ala Gly Pro Gly Ser Gly Ile Tyr Gly Pro Gly Ala Ser Gly 485 490 495 Ile Asn Gly Pro Gly Ser Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro<00=3369>500 505 510 Gly Ile Ser Ala Ala Ala Ala Ala Gly Ile Tyr Val Leu Gly Pro Gly 515 520 525 Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 530 535 540 Ile Tyr Gly Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ile 545 550 555 560 Ser Gly Ser Gly Val Leu Gly Pro Gly Val Leu Gly Pro Tyr Ala Ser 565 570 575 Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Leu Gly Pro Gly Ala 580 585 590 Ser <210> 28 <211> 590 <212> PRT <213> Artificial Sequence <220> <223> Met-PRT916 <400> 28 Met Gly Pro Gly Val Ile Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Gly Leu Asn Gly Pro Gly Ser Gly Val Ile Gly Pro Gly 20 25 30 Leu Ser Gly Leu Tyr Gly Pro Gly Val Ile Gly Pro Gly Val Ile Gly 35 40 45 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Leu Tyr Gly Pro 50 55 60 Gly Val Ile Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 65 70 75 80 Ser Gly Val Ile Gly Pro Gly Ala Ser Gly Leu Tyr Gly Pro Gly Val 85 90 95 Ile Gly Pro Gly Val Ile Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 100 105 110 Gly Leu Tyr Gly Ser Gly Pro Gly Val Ile Gly Pro Tyr Gly Ser Ala 115 120 125 Ala Ala Ala Ala Gly Pro Gly Ser Gly Leu Tyr Gly Leu Gly Pro Tyr 130 135 140 Gly Pro Gly Ala Ser Gly Pro Gly Leu Tyr Gly Pro Gly Val Ile Gly 145 150 155 160 Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Val Ile Gly Pro 165 170 175 Gly Leu Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Leu Tyr 180 185 190 Gly Ser Gly Pro Gly Val Ile Gly Pro Tyr Gly Pro Gly Leu Ser Gly 195 200 205 Ser Gly Val Ile Gly Pro Gly Val Ile Gly Pro Tyr Ala Ser Ala Ala 210 215 220 Ala Ala Ala Gly Pro Gly Val Ile Gly Pro Tyr Gly Pro Gly Ser Ser 225 230 235 240 Ala Ala Ala Ala Ala Gly Leu Tyr Gly Tyr Gly Pro Gly Val Ile Gly 245 250 255 Pro Tyr Gly Pro Gly Ala Ser Gly Leu Asn Gly Pro Gly Ser Gly Leu 260 265 270 Tyr Gly Pro Gly Val Ile Gly Pro Gly Leu Ser Ala Ala Ala Ala Ala 275 280 285 Gly Pro Gly Val Ile Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 290 295 300 Ala Ala Gly Leu Tyr Gly Pro Gly Val Ile Gly Pro Gly Leu Tyr Gly 305 310 315 320 Pro Gly Ser Ser Gly Pro Gly Val Ile Gly Pro Tyr Gly Pro Gly Ser 325 330 335 Ser Ala Ala Ala Ala Ala Gly Leu Tyr Gly Pro Gly Val Ile Gly Pro 340 345 350 Tyr Gly Pro Gly Leu Ser Ala Ala Ala Ala Ala Gly Leu Tyr Val Ile 355 360 365 Gly Pro Gly Val Ile Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly 370 375 380 Val Ile Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 385 390 395 400 Pro Gly Leu Tyr Gly Pro Gly Val Ile Gly Pro Ser Ala Ser Ala Ala 405 410 415 Ala Ala Ala Gly Leu Tyr Gly Ser Gly Pro Gly Leu Tyr Gly Pro Tyr 420 425 430 Gly Pro Gly Leu Ser Gly Pro Gly Ser Gly Val Ile Gly Leu Gly Pro 435 440 445 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Leu Tyr Gly Pro 450 455 460 Gly Val Ile Gly Pro Tyr Gly Pro Gly Leu Ser Ala Ala Ala Ala Ala 465 470 475 480 Gly Pro Gly Ser Gly Leu Tyr Gly Pro Gly Ala Ser Gly Leu Asn Gly 485 490 495 Pro Gly Ser Gly Leu Tyr Gly Pro Gly Val Ile Gly Pro Gly Leu Ser 500 505 510 Ala Ala Ala Ala Ala Gly Leu Tyr Val Ile Gly Pro Gly Val Ile Gly 515 520 525 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Leu Tyr Gly 530 535 540 Ser Gly Pro Gly Val Ile Gly Pro Tyr Gly Pro Gly Leu Ser Gly Ser 545 550 555 560 Gly Val Ile Gly Pro Gly Val Ile Gly Pro Tyr Ala Ser Ala Ala Ala 565 570 575 Ala Ala Gly Pro Gly Ser Gly Val Ile Gly Pro Gly Ala Ser 580 585 590 <210> 29 <211> 590 <212> PRT <213> Artificial Sequence <220> <223> Met-PRT918 <400> 29 Met Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Gly Ile Asn Gly Pro Gly Ser Gly Val Phe Gly Pro Gly 20 25 30 Ile Ser Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Gly Val Phe Gly 35 40 45 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Ile Tyr Gly Pro 50 55 60 Gly Val Phe Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 65 70 75 80 Ser Gly Val Phe Gly Pro Gly Ala Ser Gly Ile Tyr Gly Pro Gly Val 85 90 95 Phe Gly Pro Gly Val Phe Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 100 105 110 Gly Ile Tyr Gly Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly Ser Ala 115 120 125 Ala Ala Ala Ala Gly Pro Gly Ser Gly Ile Tyr Gly Ile Gly Pro Tyr 130 135 140 Gly Pro Gly Ala Ser Gly Pro Gly Ile Tyr Gly Pro Gly Val Phe Gly 145 150 155 160 Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Val Phe Gly Pro 165 170 175 Gly Ile Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr 180 185 190 Gly Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ile Ser Gly 195 200 205 Ser Gly Val Phe Gly Pro Gly Val Phe Gly Pro Tyr Ala Ser Ala Ala 210 215 220 Ala Ala Ala Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ser Ser 225 230 235 240 Ala Ala Ala Ala Ala Gly Ile Tyr Gly Tyr Gly Pro Gly Val Phe Gly 245 250 255 Pro Tyr Gly Pro Gly Ala Ser Gly Ile Asn Gly Pro Gly Ser Gly Ile 260 265 270 Tyr Gly Pro Gly Val Phe Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala 275 280 285 Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 290 295 300 Ala Ala Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Gly Ile Tyr Gly 305 310 315 320 Pro Gly Ser Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ser 325 330 335 Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro 340 345 350 Tyr Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala Gly Ile Tyr Val Phe 355 360 365 Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly 370 375 380 Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 385 390 395 400 Pro Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Ser Ala Ser Ala Ala 405 410 415 Ala Ala Ala Gly Ile Tyr Gly Ser Gly Pro Gly Ile Tyr Gly Pro Tyr 420 425 430 Gly Pro Gly Ile Ser Gly Pro Gly Ser Gly Val Phe Gly Ile Gly Pro 435 440 445 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Pro 450 455 460 Gly Val Phe Gly Pro Tyr Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala 465 470 475 480 Gly Pro Gly Ser Gly Ile Tyr Gly Pro Gly Ala Ser Gly Ile Asn Gly 485 490 495 Pro Gly Ser Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Gly Ile Ser 500 505 510 Ala Ala Ala Ala Ala Gly Ile Tyr Val Phe Gly Pro Gly Val Phe Gly 515 520 525 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly 530 535 540 Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ile Ser Gly Ser 545 550 555 560 Gly Val Phe Gly Pro Gly Val Phe Gly Pro Tyr Ala Ser Ala Ala Ala 565 570 575 Ala Ala Gly Pro Gly Ser Gly Val Phe Gly Pro Gly Ala Ser 580 585 590 <210> 30 <211> 565 <212> PRT <213> Artificial Sequence <220> <223> Met-PRT699 <400> 30 Met Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Gly Ser Asn Gly Pro Gly Ser Gly Val Leu Gly 20 25 30 Pro Gly Gln Ser Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro Gly Val 35 40 45 Leu Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly 50 55 60 Gln Tyr Gly Pro Gly Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala 65 70 75 80 Ala Ala Ala Gly Pro Gly Ser Gly Val Leu Gly Pro Gly Ala Ser Gly 85 90 95 Gln Tyr Gly Pro Gly Val Leu Gly Pro Gly Val Leu Gly Pro Gly Ser 100 105 110 Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly 115 120 125 Val Leu Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro 130 135 140 Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly 145 150 155 160 Pro Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro Ser Ala Ser Ala Ala 165 170 175 Ala Ala Ala Ala Ala Gly Ser Gly Val Leu Gly Pro Gly Gln Tyr Gly 180 185 190 Pro Tyr Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser 195 200 205 Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly 210 215 220 Val Leu Gly Pro Gly Val Leu Gly Pro Tyr Ala Ser Ala Ala Ala Ala 225 230 235 240 Ala Ala Ala Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ser Ser 245 250 255 Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Tyr Gly Pro Gly Val 260 265 270 Leu Gly Pro Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser 275 280 285 Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro Gly Pro Ser Ala Ala Ala 290 295 300 Ala Ala Ala Ala Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala 305 310 315 320 Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Val Leu 325 330 335 Gly Pro Gly Gln Tyr Gly Pro Gly Ser Ser Gly Pro Gly Val Leu Gly 340 345 350 Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser 355 360 365 Tyr Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Pro Ser Ala Ala 370 375 380 Ala Ala Ala Ala Ala Gly Ser Tyr Val Leu Gly Pro Gly Val Leu Gly 385 390 395 400 Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly 405 410 415 Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr 420 425 430 Gly Pro Gly Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala 435 440 445 Ala Gly Ser Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro 450 455 460 Gly Gln Ser Gly Pro Gly Ser Gly Val Leu Gly Gln Gly Pro Tyr Gly 465 470 475 480 Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro 485 490 495 Gly Val Leu Gly Pro Tyr Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala 500 505 510 Ala Ala Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln 515 520 525 Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro Gly 530 535 540 Pro Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Leu 545 550 555 560 Gly Pro Gly Ala Ser 565 <210> 31 <211> 565 <212> PRT <213> Artificial Sequence <220> <223> Met-PRT698 <400> 31 Met Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Ala Ala Gly Ser Asn Gly Pro Gly Ser Gly Val Leu Gly 20 25 30 Pro Gly Ile Ser Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro Gly Val 35 40 45 Leu Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly 50 55 60 Ile Tyr Gly Pro Gly Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala 65 70 75 80 Ala Ala Ala Gly Pro Gly Ser Gly Val Leu Gly Pro Gly Ala Ser Gly 85 90 95 Ile Tyr Gly Pro Gly Val Leu Gly Pro Gly Val Leu Gly Pro Gly Ser 100 105 110 Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly 115 120 125 Val Leu Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro 130 135 140 Gly Ser Gly Ile Tyr Gly Ile Gly Pro Tyr Gly Pro Gly Ala Ser Gly 145 150 155 160 Pro Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro Ser Ala Ser Ala Ala 165 170 175 Ala Ala Ala Ala Ala Gly Ser Gly Val Leu Gly Pro Gly Ile Tyr Gly 180 185 190 Pro Tyr Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser 195 200 205 Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ile Ser Gly Ser Gly 210 215 220 Val Leu Gly Pro Gly Val Leu Gly Pro Tyr Ala Ser Ala Ala Ala Ala 225 230 235 240 Ala Ala Ala Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ser Ser 245 250 255 Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Tyr Gly Pro Gly Val 260 265 270 Leu Gly Pro Tyr Gly Pro Gly Ala Ser Gly Ile Asn Gly Pro Gly Ser 275 280 285 Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro Gly Pro Ser Ala Ala Ala 290 295 300 Ala Ala Ala Ala Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala 305 310 315 320 Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Val Leu 325 330 335 Gly Pro Gly Ile Tyr Gly Pro Gly Ser Ser Gly Pro Gly Val Leu Gly 340 345 350 Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser 355 360 365 Tyr Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Pro Ser Ala Ala 370 375 380 Ala Ala Ala Ala Ala Gly Ser Tyr Val Leu Gly Pro Gly Val Leu Gly 385 390 395 400 Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly 405 410 415 Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Ile Tyr 420 425 430 Gly Pro Gly Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala 435 440 445 Ala Gly Ser Tyr Gly Ser Gly Pro Gly Ile Tyr Gly Pro Tyr Gly Pro 450 455 460 Gly Ile Ser Gly Pro Gly Ser Gly Val Leu Gly Ile Gly Pro Tyr Gly 465 470 475 480 Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro 485 490 495 Gly Val Leu Gly Pro Tyr Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala 500 505 510 Ala Ala Gly Pro Gly Ser Gly Ile Tyr Gly Pro Gly Ala Ser Gly Ile 515 520 525 Asn Gly Pro Gly Ser Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro Gly 530 535 540 Pro Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Leu 545 550 555 560 Gly Pro Gly Ala Ser 565 <210> 32 <211> 1179 <212> PRT <213> Artificial sequence <220> <223> Met-PRT966 <400> 32 Met Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Gly Ile Asn Gly Pro Gly Ser Gly Val Phe Gly Pro Gly 20 25 30 Ile Ser Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Gly Val Phe Gly 35 40 45 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Ile Tyr Gly Pro 50 55 60 Gly Val Phe Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 65 70 75 80 Ser Gly Val Phe Gly Pro Gly Ala Ser Gly Ile Tyr Gly Pro Gly Val 85 90 95 Phe Gly Pro Gly Val Phe Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 100 105 110 Gly Ile Tyr Gly Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly Ser Ala 115 120 125 Ala Ala Ala Ala Gly Pro Gly Ser Gly Ile Tyr Gly Ile Gly Pro Tyr 130 135 140 Gly Pro Gly Ala Ser Gly Pro Gly Ile Tyr Gly Pro Gly Val Phe Gly 145 150 155 160 Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Val Phe Gly Pro 165 170 175 Gly Ile Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr 180 185 190 Gly Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ile Ser Gly 195 200 205 Ser Gly Val Phe Gly Pro Gly Val Phe Gly Pro Tyr Ala Ser Ala Ala 210 215 220 Ala Ala Ala Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ser Ser 225 230 235 240 Ala Ala Ala Ala Ala Gly Ile Tyr Gly Tyr Gly Pro Gly Val Phe Gly 245 250 255 Pro Tyr Gly Pro Gly Ala Ser Gly Ile Asn Gly Pro Gly Ser Gly Ile 260 265 270 Tyr Gly Pro Gly Val Phe Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala 275 280 285 Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 290 295 300 Ala Ala Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Gly Ile Tyr Gly 305 310 315 320 Pro Gly Ser Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ser 325 330 335 Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro 340 345 350 Tyr Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala Gly Ile Tyr Val Phe 355 360 365 Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly 370 375 380 Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 385 390 395 400 Pro Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Ser Ala Ser Ala Ala 405 410 415 Ala Ala Ala Gly Ile Tyr Gly Ser Gly Pro Gly Ile Tyr Gly Pro Tyr 420 425 430 Gly Pro Gly Ile Ser Gly Pro Gly Ser Gly Val Phe Gly Ile Gly Pro 435 440 445 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Pro 450 455 460 Gly Val Phe Gly Pro Tyr Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala 465 470 475 480 Gly Pro Gly Ser Gly Ile Tyr Gly Pro Gly Ala Ser Gly Ile Asn Gly 485 490 495 Pro Gly Ser Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Gly Ile Ser 500 505 510 Ala Ala Ala Ala Ala Gly Ile Tyr Val Phe Gly Pro Gly Val Phe Gly 515 520 525 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly 530 535 540 Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ile Ser Gly Ser 545 550 555 560 Gly Val Phe Gly Pro Gly Val Phe Gly Pro Tyr Ala Ser Ala Ala Ala 565 570 575 Ala Ala Gly Pro Gly Ser Gly Val Phe Gly Pro Gly Ala Ser Gly Pro 580 585 590 Gly Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala 595 600 605 Gly Ile Asn Gly Pro Gly Ser Gly Val Phe Gly Pro Gly Ile Ser Gly 610 615 620 Ile Tyr Gly Pro Gly Val Phe Gly Pro Gly Val Phe Gly Pro Gly Ser 625 630 635 640 Ser Ala Ala Ala Ala Ala Gly Pro Gly Ile Tyr Gly Pro Gly Val Phe 645 650 655 Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val 660 665 670 Phe Gly Pro Gly Ala Ser Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro 675 680 685 Gly Val Phe Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Ile Tyr 690 695 700 Gly Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly Ser Ala Ala Ala Ala 705 710 715 720 Ala Gly Pro Gly Ser Gly Ile Tyr Gly Ile Gly Pro Tyr Gly Pro Gly 725 730 735 Ala Ser Gly Pro Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Ser Ala 740 745 750 Ser Ala Ala Ala Ala Ala Gly Ser Gly Val Phe Gly Pro Gly Ile Tyr 755 760 765 Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser Gly 770 775 780 Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ile Ser Gly Ser Gly Val 785 790 795 800 Phe Gly Pro Gly Val Phe Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala 805 810 815 Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala 820 825 830 Ala Ala Gly Ile Tyr Gly Tyr Gly Pro Gly Val Phe Gly Pro Tyr Gly 835 840 845 Pro Gly Ala Ser Gly Ile Asn Gly Pro Gly Ser Gly Ile Tyr Gly Pro 850 855 860 Gly Val Phe Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala Gly Pro Gly 865 870 875 880 Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 885 890 895 Ile Tyr Gly Pro Gly Val Phe Gly Pro Gly Ile Tyr Gly Pro Gly Ser 900 905 910 Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala 915 920 925 Ala Ala Ala Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro 930 935 940 Gly Ile Ser Ala Ala Ala Ala Ala Gly Ile Tyr Val Phe Gly Pro Gly 945 950 955 960 Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Val Phe Gly 965 970 975 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ile 980 985 990 Tyr Gly Pro Gly Val Phe Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala 995 1000 1005 Gly Ile Tyr Gly Ser Gly Pro Gly Ile Tyr Gly Pro Tyr Gly Pro 1010 1015 1020 Gly Ile Ser Gly Pro Gly Ser Gly Val Phe Gly Ile Gly Pro Tyr 1025 1030 1035 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Pro 1040 1045 1050 Gly Val Phe Gly Pro Tyr Gly Pro Gly Ile Ser Ala Ala Ala Ala 1055 1060 1065 Ala Gly Pro Gly Ser Gly Ile Tyr Gly Pro Gly Ala Ser Gly Ile 1070 1075 1080 Asn Gly Pro Gly Ser Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro 1085 1090 1095 Gly Ile Ser Ala Ala Ala Ala Ala Gly Ile Tyr Val Phe Gly Pro 1100 1105 1110 Gly Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala 1115 1120 1125 Ala Gly Ile Tyr Gly Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly 1130 1135 1140 Pro Gly Ile Ser Gly Ser Gly Val Phe Gly Pro Gly Val Phe Gly 1145 1150 1155 Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val 1160 1165 1170 Phe Gly Pro Gly Ala Ser 1175 <210> 33 <211> 601 <212> PRT <213> Artificial Sequence <220> <223> PRT888 <400> 33 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Val 1 5 10 15 Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln 20 25 30 Asn Gly Pro Gly Ser Gly Val Leu Gly Pro Gly Gln Ser Gly Gln Tyr 35 40 45 Gly Pro Gly Val Leu Gly Pro Gly Val Leu Gly Pro Gly Ser Ser Ala 50 55 60 Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro 65 70 75 80 Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Leu Gly 85 90 95 Pro Gly Ala Ser Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro Gly Val 100 105 110 Leu Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser 115 120 125 Gly Pro Gly Val Leu Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly 130 135 140 Pro Gly Ser Gly Gln Tyr Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser 145 150 155 160 Gly Pro Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro Ser Ala Ser Ala 165 170 175 Ala Ala Ala Ala Gly Ser Gly Val Leu Gly Pro Gly Gln Tyr Gly Pro 180 185 190 Tyr Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly 195 200 205 Val Leu Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Val Leu Gly 210 215 220 Pro Gly Val Leu Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro 225 230 235 240 Gly Val Leu Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 245 250 255 Gly Gln Tyr Gly Tyr Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly 260 265 270 Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro Gly Val 275 280 285 Leu Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly Val Leu 290 295 300 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr 305 310 315 320 Gly Pro Gly Val Leu Gly Pro Gly Gln Tyr Gly Pro Gly Ser Ser Gly 325 330 335 Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala 340 345 350 Ala Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Gln 355 360 365 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Val Leu Gly Pro Gly Val Leu 370 375 380 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Val Leu Gly Pro Tyr 385 390 395 400 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly 405 410 415 Pro Gly Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Gln 420 425 430 Tyr Gly Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro Gly Gln Ser 435 440 445 Gly Pro Gly Ser Gly Val Leu Gly Gln Gly Pro Tyr Gly Pro Gly Ala 450 455 460 Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro 465 470 475 480 Tyr Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 485 490 495 Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln 500 505 510 Tyr Gly Pro Gly Val Leu Gly Pro Gly Gln Ser Ala Ala Ala Ala Ala 515 520 525 Gly Gln Tyr Val Leu Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly 530 535 540 Ala Ser Ala Ala Ala Ala Ala Gly Gln Tyr Gly Ser Gly Pro Gly Val 545 550 555 560 Leu Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Val Leu Gly Pro 565 570 575 Gly Val Leu Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 580 585 590 Ser Gly Val Leu Gly Pro Gly Ala Ser 595 600 <210> 34 <211> 601 <212> PRT <213> Artificial Sequence <220><000​​​​Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Thr 1 5 10 15 Ser Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ala 20 25 30 Asn Gly Pro Gly Ser Gly Thr Ser Gly Pro Gly Ala Ser Gly Ala Tyr 35 40 45 Gly Pro Gly Thr Ser Gly Pro Gly Thr Ser Gly Pro Gly Ser Ser Ala 50 55 60 Ala Ala Ala Ala Gly Pro Gly Ala Tyr Gly Pro Gly Thr Ser Gly Pro 65 70 75 80 Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Thr Ser Gly 85 90 95 Pro Gly Ala Ser Gly Ala Tyr Gly Pro Gly Thr Ser Gly Pro Gly Thr 100 105 110 Ser Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Ala Tyr Gly Ser 115 120 125 Gly Pro Gly Thr Ser Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly 130 135 140 Pro Gly Ser Gly Ala Tyr Gly Ala Gly Pro Tyr Gly Pro Gly Ala Ser 145 150 155 160 Gly Pro Gly Ala Tyr Gly Pro Gly Thr Ser Gly Pro Ser Ala Ser Ala 165 170 175 Ala Ala Ala Ala Gly Ser Gly Thr Ser Gly Pro Gly Ala Tyr Gly Pro 180 185 190 Tyr Ala Ser Ala Ala Ala Ala Ala Gly Ala Tyr Gly Ser Gly Pro Gly 195 200 205 Thr Ser Gly Pro Tyr Gly Pro Gly Ala Ser Gly Ser Gly Thr Ser Gly 210 215 220 Pro Gly Thr Ser Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro 225 230 235 240 Gly Thr Ser Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 245 250 255 Gly Ala Tyr Gly Tyr Gly Pro Gly Thr Ser Gly Pro Tyr Gly Pro Gly 260 265 270 Ala Ser Gly Ala Asn Gly Pro Gly Ser Gly Ala Tyr Gly Pro Gly Thr 275 280 285 Ser Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Thr Ser 290 295 300 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ala Tyr 305 310 315 320 Gly Pro Gly Thr Ser Gly Pro Gly Ala Tyr Gly Pro Gly Ser Ser Gly 325 330 335 Pro Gly Thr Ser Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala 340 345 350 Ala Gly Ala Tyr Gly Pro Gly Thr Ser Gly Pro Tyr Gly Pro Gly Ala 355 360 365 Ser Ala Ala Ala Ala Ala Gly Ala Tyr Thr Ser Gly Pro Gly Thr Ser 370 375 380 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Thr Ser Gly Pro Tyr 385 390 395 400 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ala Tyr Gly 405 410 415 Pro Gly Thr Ser Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ala 420 425 430 Tyr Gly Ser Gly Pro Gly Ala Tyr Gly Pro Tyr Gly Pro Gly Ala Ser 435 440 445 Gly Pro Gly Ser Gly Thr Ser Gly Ala Gly Pro Tyr Gly Pro Gly Ala 450 455 460 Ser Ala Ala Ala Ala Ala Gly Ala Tyr Gly Pro Gly Thr Ser Gly Pro 465 470 475 480 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 485 490 495 Ala Tyr Gly Pro Gly Ala Ser Gly Ala Asn Gly Pro Gly Ser Gly Ala 500 505 510 Tyr Gly Pro Gly Thr Ser Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala 515 520 525 Gly Ala Tyr Thr Ser Gly Pro Gly Thr Ser Gly Pro Tyr Gly Pro Gly 530 535 540 Ala Ser Ala Ala Ala Ala Ala Gly Ala Tyr Gly Ser Gly Pro Gly Thr 545 550 555 560 Ser Gly Pro Tyr Gly Pro Gly Ala Ser Gly Ser Gly Thr Ser Gly Pro 565 570 575 Gly Thr Ser Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 580 585 590 Ser Gly Thr Ser Gly Pro Gly Ala Ser �95 600 <210> 35 <211> 601 <212> PRT <213> Artificial Sequence <220> <223> PRT889 <400> 35 Met His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Val 1 5 10 15 Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile 20 25 30 Asn Gly Pro Gly Ser Gly Val Leu Gly Pro Gly Ile Ser Gly Ile Tyr 35 40 45 Gly Pro Gly Val Leu Gly Pro Gly Val Leu Gly Pro Gly Ser Ser Ala 50 55 60 Ala Ala Ala Ala Gly Pro Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro 65 70 75 80 Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Leu Gly 85 90 95 Pro Gly Ala Ser Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro Gly Val 100 105 110 Leu Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser 115 120 125 Gly Pro Gly Val Leu Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly 130 135 140 Pro Gly Ser Gly Ile Tyr Gly Ile Gly Pro Tyr Gly Pro Gly Ala Ser 145 150 155 160 Gly Pro Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro Ser Ala Ser Ala 165 170 175 Ala Ala Ala Ala Gly Ser Gly Val Leu Gly Pro Gly Ile Tyr Gly Pro 180 185 190 Tyr Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser Gly Pro Gly 195 200 205 Val Leu Gly Pro Tyr Gly Pro Gly Ile Ser Gly Ser Gly Val Leu Gly 210 215 220 Pro Gly Val Leu Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro 225 230 235 240 Gly Val Leu Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 245 250 255 Gly Ile Tyr Gly Tyr Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly 260 265 270 Ala Ser Gly Ile Asn Gly Pro Gly Ser Gly Ile Tyr Gly Pro Gly Val 275 280 285 Leu Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala Gly Pro Gly Val Leu 290 295 300 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr 305 310 315 320 Gly Pro Gly Val Leu Gly Pro Gly Ile Tyr Gly Pro Gly Ser Ser Gly 325 330 335 Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala 340 345 350 Ala Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ile 355 360 365 Ser Ala Ala Ala Ala Ala Gly Ile Tyr Val Leu Gly Pro Gly Val Leu 370 375 380 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Val Leu Gly Pro Tyr 385 390 395 400 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ile Tyr Gly 405 410 415 Pro Gly Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ile 420 425 430 Tyr Gly Ser Gly Pro Gly Ile Tyr Gly Pro Tyr Gly Pro Gly Ile Ser 435 440 445 Gly Pro Gly Ser Gly Val Leu Gly Ile Gly Pro Tyr Gly Pro Gly Ala 450 455 460 Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro 465 470 475 480 Tyr Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 485 490 495 Ile Tyr Gly Pro Gly Ala Ser Gly Ile Asn Gly Pro Gly Ser Gly Ile 500 505 510 Tyr Gly Pro Gly Val Leu Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala 515 520 525 Gly Ile Tyr Val Leu Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly 530 535 540 Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser Gly Pro Gly Val 545 550 555 560 Leu Gly Pro Tyr Gly Pro Gly Ile Ser Gly Ser Gly Val Leu Gly Pro 565 570 575 Gly Val Leu Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 580 585 590 Ser Gly Val Leu Gly Pro Gly Ala Ser 595 600 <210> 36 <211> 601 <212> PRT <213> Artificial Sequence <220> <223> PRT916 <400> 36 Met His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Val 1 5 10 15 Ile Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Leu 20 25 30 Asn Gly Pro Gly Ser Gly Val Ile Gly Pro Gly Leu Ser Gly Leu Tyr 35 40 45 Gly Pro Gly Val Ile Gly Pro Gly Val Ile Gly Pro Gly Ser Ser Ala 50 55 60 Ala Ala Ala Ala Gly Pro Gly Leu Tyr Gly Pro Gly Val Ile Gly Pro 65 70 75 80 Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Ile Gly 85 90 95 Pro Gly Ala Ser Gly Leu Tyr Gly Pro Gly Val Ile Gly Pro Gly Val 100 105 110 Ile Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Leu Tyr Gly Ser 115 120 125 Gly Pro Gly Val Ile Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly 130 135 140 Pro Gly Ser Gly Leu Tyr Gly Leu Gly Pro Tyr Gly Pro Gly Ala Ser 145 150 155 160 Gly Pro Gly Leu Tyr Gly Pro Gly Val Ile Gly Pro Ser Ala Ser Ala 165 170 175 Ala Ala Ala Ala Gly Ser Gly Val Ile Gly Pro Gly Leu Tyr Gly Pro 180 185 190 Tyr Ala Ser Ala Ala Ala Ala Ala Gly Leu Tyr Gly Ser Gly Pro Gly 195 200 205 Val Ile Gly Pro Tyr Gly Pro Gly Leu Ser Gly Ser Gly Val Ile Gly 210 215 220 Pro Gly Val Ile Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro 225 230 235 240 Gly Val Ile Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 245 250 255 Gly Leu Tyr Gly Tyr Gly Pro Gly Val Ile Gly Pro Tyr Gly Pro Gly 260 265 270 Ala Ser Gly Leu Asn Gly Pro Gly Ser Gly Leu Tyr Gly Pro Gly Val 275 280 285 Ile Gly Pro Gly Leu Ser Ala Ala Ala Ala Ala Gly Pro Gly Val Ile 290 295 300 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Leu Tyr 305 310 315 320 Gly Pro Gly Val Ile Gly Pro Gly Leu Tyr Gly Pro Gly Ser Ser Gly 325 330 335 Pro Gly Val Ile Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala 340 345 350 Ala Gly Leu Tyr Gly Pro Gly Val Ile Gly Pro Tyr Gly Pro Gly Leu 355 360 365 Ser Ala Ala Ala Ala Ala Gly Leu Tyr Val Ile Gly Pro Gly Val Ile 370 375 380 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Val Ile Gly Pro Tyr 385 390 395 400 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Leu Tyr Gly 405 410 415 Pro Gly Val Ile Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Leu 420 425 430 Tyr Gly Ser Gly Pro Gly Leu Tyr Gly Pro Tyr Gly Pro Gly Leu Ser 435 440 445 Gly Pro Gly Ser Gly Val Ile Gly Leu Gly Pro Tyr Gly Pro Gly Ala 450 455 460 Ser Ala Ala Ala Ala Ala Gly Leu Tyr Gly Pro Gly Val Ile Gly Pro 465 470 475 480 Tyr Gly Pro Gly Leu Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 485 490 495 Leu Tyr Gly Pro Gly Ala Ser Gly Leu Asn Gly Pro Gly Ser Gly Leu 500 505 510 Tyr Gly Pro Gly Val Ile Gly Pro Gly Leu Ser Ala Ala Ala Ala Ala 515 520 525 Gly Leu Tyr Val Ile Gly Pro Gly Val Ile Gly Pro Tyr Gly Pro Gly 530 535 540 Ala Ser Ala Ala Ala Ala Ala Gly Leu Tyr Gly Ser Gly Pro Gly Val 545 550 555 560 Ile Gly Pro Tyr Gly Pro Gly Leu Ser Gly Ser Gly Val Ile Gly Pro 565 570 575 Gly Val Ile Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 580 585 590 Ser Gly Val Ile Gly Pro Gly Ala Ser 595 600 <210> 37 <211> 601 <212> PRT <213> Artificial Sequence <220> <223> PRT918 <400> 37 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Val 1 5 10 15 Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile 20 25 30 Asn Gly Pro Gly Ser Gly Val Phe Gly Pro Gly Ile Ser Gly Ile Tyr 35 40 45 Gly Pro Gly Val Phe Gly Pro Gly Val Phe Gly Pro Gly Ser Ser Ala 50 55 60 Ala Ala Ala Ala Gly Pro Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro 65 70 75 80 Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Phe Gly 85 90 95 Pro Gly Ala Ser Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Gly Val 100 105 110 Phe Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser 115 120 125 Gly Pro Gly Val Phe Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly 130 135 140 Pro Gly Ser Gly Ile Tyr Gly Ile Gly Pro Tyr Gly Pro Gly Ala Ser 145 150 155 160 Gly Pro Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Ser Ala Ser Ala 165 170 175 Ala Ala Ala Ala Gly Ser Gly Val Phe Gly Pro Gly Ile Tyr Gly Pro 180 185 190 Tyr Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser Gly Pro Gly 195 200 205 Val Phe Gly Pro Tyr Gly Pro Gly Ile Ser Gly Ser Gly Val Phe Gly 210 215 220 Pro Gly Val Phe Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro 225 230 235 240 Gly Val Phe Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 245 250 255 Gly Ile Tyr Gly Tyr Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly 260 265 270 Ala Ser Gly Ile Asn Gly Pro Gly Ser Gly Ile Tyr Gly Pro Gly Val 275 280 285 Phe Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala Gly Pro Gly Val Phe 290 295 300 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr 305 310 315 320 Gly Pro Gly Val Phe Gly Pro Gly Ile Tyr Gly Pro Gly Ser Ser Gly 325 330 335 Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala 340 345 350 Ala Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ile 355 360 365 Ser Ala Ala Ala Ala Ala Gly Ile Tyr Val Phe Gly Pro Gly Val Phe 370 375 380 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Val Phe Gly Pro Tyr 385 390 395 400 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ile Tyr Gly 405 410 415 Pro Gly Val Phe Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ile 420 425 430 Tyr Gly Ser Gly Pro Gly Ile Tyr Gly Pro Tyr Gly Pro Gly Ile Ser 435 440 445 Gly Pro Gly Ser Gly Val Phe Gly Ile Gly Pro Tyr Gly Pro Gly Ala 450 455 460 Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro 465 470 475 480 Tyr Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 485 490 495 Ile Tyr Gly Pro Gly Ala Ser Gly Ile Asn Gly Pro Gly Ser Gly Ile 500 505 510 Tyr Gly Pro Gly Val Phe Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala 515 520 525 Gly Ile Tyr Val Phe Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly 530 535 540 Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser Gly Pro Gly Val 545 550 555 560 Phe Gly Pro Tyr Gly Pro Gly Ile Ser Gly Ser Gly Val Phe Gly Pro 565 570 575 Gly Val Phe Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 580 585 590 Ser Gly Val Phe Gly Pro Gly Ala Ser 595 600 <210> 38 <211> 576 <212> PRT <213> Artificial Sequence <220> <223> PRT699 <400> 38 Met His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Val 1 5 10 15 Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala 20 25 30 Gly Ser Asn Gly Pro Gly Ser Gly Val Leu Gly Pro Gly Gln Ser Gly 35 40 45 Gln Tyr Gly Pro Gly Val Leu Gly Pro Gly Val Leu Gly Pro Gly Ser 50 55 60 Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly 65 70 75 80 Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro 85 90 95 Gly Ser Gly Val Leu Gly Pro Gly Ala Ser Gly Gln Tyr Gly Pro Gly 100 105 110 Val Leu Gly Pro Gly Val Leu Gly Pro Gly Ser Ser Ala Ala Ala Ala 115 120 125 Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly Val Leu Gly Pro Tyr 130 135 140 Gly Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Gln Tyr 145 150 155 160 Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Gln Tyr Gly 165 170 175 Pro Gly Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala 180 185 190 Gly Ser Gly Val Leu Gly Pro Gly Gln Tyr Gly Pro Tyr Ala Ser Ala 195 200 205 Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly Val Leu 210 215 220 Gly Pro Tyr Gly Pro Gly Gln Ser Gly Ser Gly Val Leu Gly Pro Gly 225 230 235 240 Val Leu Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Pro 245 250 255 Gly Val Leu Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 260 265 270 Ala Ala Gly Ser Tyr Gly Tyr Gly Pro Gly Val Leu Gly Pro Tyr Gly 275 280 285 Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser Gly Gln Tyr Gly Pro 290 295 300 Gly Val Leu Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly 305 310 315 320 Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala 325 330 335 Ala Ala Ala Gly Ser Tyr Gly Pro Gly Val Leu Gly Pro Gly Gln Tyr 340 345 350 Gly Pro Gly Ser Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly 355 360 365 Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Val 370 375 380 Leu Gly Pro Tyr Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala 385 390 395 400 Gly Ser Tyr Val Leu Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly 405 410 415 Ala Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala 420 425 430 Ala Ala Ala Ala Ala Ala Gly Pro Gly Gln Tyr Gly Pro Gly Val Leu 435 440 445 Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly 450 455 460 Ser Gly Pro Gly Gln Tyr Gly Pro Tyr Gly Pro Gly Gln Ser Gly Pro 465 470 475 480 Gly Ser Gly Val Leu Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ser Ala 485 490 495 Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Val Leu Gly Pro 500 505 510 Tyr Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly 515 520 525 Ser Gly Gln Tyr Gly Pro Gly Ala Ser Gly Gln Asn Gly Pro Gly Ser 530 535 540 Gly Gln Tyr Gly Pro Gly Val Leu Gly Pro Gly Pro Ser Ala Ala Ala 545 550 555 560 Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Leu Gly Pro Gly Ala Ser 565 570 575 <CitationRef> 39 <CitationRef> 576 <CitationRef> PRT <CitationRef> Artificial Sequence <CitationRef>[[]]<0 / 0> <CitationRef> PRT698 <CitationRef> 39 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Val 1 5 10 15 Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Ala Ala 20 25 30 Note: There seems to be an unclear tag <220> in the original. I've translated it as <CitationRef>[[]]<0 / 0> as per the instruction to preserve tags exactly. If this is incorrect, more context is needed to provide a more accurate translation for that specific tag.Gly Ser Asn Gly Pro Gly Ser Gly Val Leu Gly Pro Gly Ile Ser Gly 35 40 45 Ile Tyr Gly Pro Gly Val Leu Gly Pro Gly Val Leu Gly Pro Gly Ser 50 55 60 Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Ile Tyr Gly Pro Gly 65 70 75 80 Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro 85 90 95 Gly Ser Gly Val Leu Gly Pro Gly Ala Ser Gly Ile Tyr Gly Pro Gly 100 105 110 Val Leu Gly Pro Gly Val Leu Gly Pro Gly Ser Ser Ala Ala Ala Ala 115 120 125 Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly Val Leu Gly Pro Tyr 130 135 140 Gly Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Ile Tyr 145 150 155 160 Gly Ile Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Ile Tyr Gly 165 170 175 Pro Gly Val Leu Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala 180 185 190 Gly Ser Gly Val Leu Gly Pro Gly Ile Tyr Gly Pro Tyr Ala Ser Ala 195 200 205 Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Ser Gly Pro Gly Val Leu 210 215 220 Gly Pro Tyr Gly Pro Gly Ile Ser Gly Ser Gly Val Leu Gly Pro Gly 225 230 235 240 Val Leu Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Pro 245 250 255 Gly Val Leu Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 260 265 270 Ala Ala Gly Ser Tyr Gly Tyr Gly Pro Gly Val Leu Gly Pro Tyr Gly 275 280 285 Pro Gly Ala Ser Gly Ile Asn Gly Pro Gly Ser Gly Ile Tyr Gly Pro 290 295 300 Gly Val Leu Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly 305 310 315 320 Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala 325 330 335 Ala Ala Ala Gly Ser Tyr Gly Pro Gly Val Leu Gly Pro Gly Ile Tyr 340 345 350 Gly Pro Gly Ser Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly 355 360 365 Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Val 370 375 380 Leu Gly Pro Tyr Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala 385 390 395 400 Gly Ser Tyr Val Leu Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly 405 410 415 Ala Ser Gly Pro Gly Val Leu Gly Pro Tyr Gly Pro Gly Ala Ser Ala 420 425 430 Ala Ala Ala Ala Ala Ala Gly Pro Gly Ile Tyr Gly Pro Gly Val Leu 435 440 445 Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly 450 455 460 Ser Gly Pro Gly Ile Tyr Gly Pro Tyr Gly Pro Gly Ile Ser Gly Pro 465 470 475 480 Gly Ser Gly Val Leu Gly Ile Gly Pro Tyr Gly Pro Gly Ala Ser Ala 485 490 495 Ala Ala Ala Ala Ala Ala Gly Ser Tyr Gly Pro Gly Val Leu Gly Pro 500 505 510 Tyr Gly Pro Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly 515 520 525 Ser Gly Ile Tyr Gly Pro Gly Ala Ser Gly Ile Asn Gly Pro Gly Ser 530 535 540 Gly Ile Tyr Gly Pro Gly Val Leu Gly Pro Gly Pro Ser Ala Ala Ala 545 550 555 560 Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Leu Gly Pro Gly Ala Ser 565 570 575 <210> 40 <211> 1190 <212> PRT <213> Artificial Sequence <220> <223> PRT966 <400> 40 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Val 1 5 10 15 Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile 20 25 30 Asn Gly Pro Gly Ser Gly Val Phe Gly Pro Gly Ile Ser Gly Ile Tyr 35 40 45 Gly Pro Gly Val Phe Gly Pro Gly Val Phe Gly Pro Gly Ser Ser Ala 50 55 60 Ala Ala Ala Ala Gly Pro Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro 65 70 75 80 Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Phe Gly 85 90 95 Pro Gly Ala Ser Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Gly Val 100 105 110 Phe Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser 115 120 125 Gly Pro Gly Val Phe Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly 130 135 140 Pro Gly Ser Gly Ile Tyr Gly Ile Gly Pro Tyr Gly Pro Gly Ala Ser 145 150 155 160 Gly Pro Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Ser Ala Ser Ala 165 170 175 Ala Ala Ala Ala Gly Ser Gly Val Phe Gly Pro Gly Ile Tyr Gly Pro 180 185 190 Tyr Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser Gly Pro Gly 195 200 205 Val Phe Gly Pro Tyr Gly Pro Gly Ile Ser Gly Ser Gly Val Phe Gly 210 215 220 Pro Gly Val Phe Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro 225 230 235 240 Gly Val Phe Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 245 250 255 Gly Ile Tyr Gly Tyr Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly 260 265 270 Ala Ser Gly Ile Asn Gly Pro Gly Ser Gly Ile Tyr Gly Pro Gly Val 275 280 285 Phe Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala Gly Pro Gly Val Phe 290 295 300 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr 305 310 315 320 Gly Pro Gly Val Phe Gly Pro Gly Ile Tyr Gly Pro Gly Ser Ser Gly 325 330 335 Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala 340 345 350 Ala Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ile 355 360 365 Ser Ala Ala Ala Ala Ala Gly Ile Tyr Val Phe Gly Pro Gly Val Phe 370 375 380 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Val Phe Gly Pro Tyr 385 390 395 400 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ile Tyr Gly 405 410 415 Pro Gly Val Phe Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ile 420 425 430 Tyr Gly Ser Gly Pro Gly Ile Tyr Gly Pro Tyr Gly Pro Gly Ile Ser 435 440 445 Gly Pro Gly Ser Gly Val Phe Gly Ile Gly Pro Tyr Gly Pro Gly Ala 450 455 460 Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro 465 470 475 480 Tyr Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 485 490 495 Ile Tyr Gly Pro Gly Ala Ser Gly Ile Asn Gly Pro Gly Ser Gly Ile 500 505 510 Tyr Gly Pro Gly Val Phe Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala 515 520 525 Gly Ile Tyr Val Phe Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly 530 535 540 Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser Gly Pro Gly Val 545 550 555 560 Phe Gly Pro Tyr Gly Pro Gly Ile Ser Gly Ser Gly Val Phe Gly Pro 565 570 575 Gly Val Phe Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 580 585 590 Ser Gly Val Phe Gly Pro Gly Ala Ser Gly Pro Gly Val Phe Gly Pro 595 600 605 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile Asn Gly Pro 610 615 620 Gly Ser Gly Val Phe Gly Pro Gly Ile Ser Gly Ile Tyr Gly Pro Gly 625 630 635 640 Val Phe Gly Pro Gly Val Phe Gly Pro Gly Ser Ser Ala Ala Ala Ala 645 650 655 Ala Gly Pro Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Ser Ala Ser 660 665 670 Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Phe Gly Pro Gly Ala 675 680 685 Ser Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Gly Val Phe Gly Pro 690 695 700 Gly Ser Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser Gly Pro Gly 705 710 715 720 Val Phe Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser 725 730 735 Gly Ile Tyr Gly Ile Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly 740 745 750 Ile Tyr Gly Pro Gly Val Phe Gly Pro Ser Ala Ser Ala Ala Ala Ala 755 760 765 Ala Gly Ser Gly Val Phe Gly Pro Gly Ile Tyr Gly Pro Tyr Ala Ser 770 775 780 Ala Ala Ala Ala Ala Gly Ile Tyr Gly Ser Gly Pro Gly Val Phe Gly 785 790 795 800 Pro Tyr Gly Pro Gly Ile Ser Gly Ser Gly Val Phe Gly Pro Gly Val 805 810 815 Phe Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Val Phe 820 825 830 Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Ile Tyr 835 840 845 Gly Tyr Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ala Ser Gly 850 855 860 Ile Asn Gly Pro Gly Ser Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro 865 870 875 880 Gly Ile Ser Ala Ala Ala Ala Ala Gly Pro Gly Val Phe Gly Pro Tyr 885 890 895 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Pro Gly 900 905 910 Val Phe Gly Pro Gly Ile Tyr Gly Pro Gly Ser Ser Gly Pro Gly Val 915 920 925 Phe Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Ile 930 935 940 Tyr Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ile Ser Ala Ala 945 950 955 960 Ala Ala Ala Gly Ile Tyr Val Phe Gly Pro Gly Val Phe Gly Pro Tyr 965 970 975 Gly Pro Gly Ala Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly 980 985 990 Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ile Tyr Gly Pro Gly Val 995 1000 1005 Phe Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly 1010 1015 1020 Ser Gly Pro Gly Ile Tyr Gly Pro Tyr Gly Pro Gly Ile Ser Gly 1025 1030 1035 Pro Gly Ser Gly Val Phe Gly Ile Gly Pro Tyr Gly Pro Gly Ala 1040 1045 1050 Ser Ala Ala Ala Ala Ala Gly Ile Tyr Gly Pro Gly Val Phe Gly 1055 1060 1065 Pro Tyr Gly Pro Gly Ile Ser Ala Ala Ala Ala Ala Gly Pro Gly 1070 1075 1080 Ser Gly Ile Tyr Gly Pro Gly Ala Ser Gly Ile Asn Gly Pro Gly 1085 1090 1095 Ser Gly Ile Tyr Gly Pro Gly Val Phe Gly Pro Gly Ile Ser Ala 1100 1105 1110 Ala Ala Ala Ala Gly Ile Tyr Val Phe Gly Pro Gly Val Phe Gly 1115 1120 1125 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Ile Tyr 1130 1135 1140 Gly Ser Gly Pro Gly Val Phe Gly Pro Tyr Gly Pro Gly Ile Ser 1145 1150 1155 Gly Ser Gly Val Phe Gly Pro Gly Val Phe Gly Pro Tyr Ala Ser 1160 1165 1170 Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Phe Gly Pro Gly 1175 1180 1185 Ala Ser 1190 <210> 41 <211> 590 <212> PRT <213> Artificial Sequence <220> <223> Met-PRT917 <400> 41 Met Gly Pro Gly Leu Ile Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Gly Val Asn Gly Pro Gly Ser Gly Leu Ile Gly Pro Gly 20 25 30 Val Ser Gly Val Tyr Gly Pro Gly Leu Ile Gly Pro Gly Leu Ile Gly 35 40 45 Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Val Tyr Gly Pro 50 55 60 Gly Leu Ile Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 65 70 75 80 Ser Gly Leu Ile Gly Pro Gly Ala Ser Gly Val Tyr Gly Pro Gly Leu 85 90 95 Ile Gly Pro Gly Leu Ile Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 100 105 110 Gly Val Tyr Gly Ser Gly Pro Gly Leu Ile Gly Pro Tyr Gly Ser Ala 115 120 125 Ala Ala Ala Ala Gly Pro Gly Ser Gly Val Tyr Gly Val Gly Pro Tyr 130 135 140 Gly Pro Gly Ala Ser Gly Pro Gly Val Tyr Gly Pro Gly Leu Ile Gly 145 150 155 160 Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Leu Ile Gly Pro 165 170 175 Gly Val Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Val Tyr 180 185 190 Gly Ser Gly Pro Gly Leu Ile Gly Pro Tyr Gly Pro Gly Val Ser Gly 195 200 205 Ser Gly Leu Ile Gly Pro Gly Leu Ile Gly Pro Tyr Ala Ser Ala Ala 210 215 220 Ala Ala Ala Gly Pro Gly Leu Ile Gly Pro Tyr Gly Pro Gly Ser Ser 225 230 235 240 Ala Ala Ala Ala Ala Gly Val Tyr Gly Tyr Gly Pro Gly Leu Ile Gly 245 250 255 Pro Tyr Gly Pro Gly Ala Ser Gly Val Asn Gly Pro Gly Ser Gly Val 260 265 270 Tyr Gly Pro Gly Leu Ile Gly Pro Gly Val Ser Ala Ala Ala Ala Ala 275 280 285 Gly Pro Gly Leu Ile Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala 290 295 300 Ala Ala Gly Val Tyr Gly Pro Gly Leu Ile Gly Pro Gly Val Tyr Gly 305 310 315 320 Pro Gly Ser Ser Gly Pro Gly Leu Ile Gly Pro Tyr Gly Pro Gly Ser 325 330 335 Ser Ala Ala Ala Ala Ala Gly Val Tyr Gly Pro Gly Leu Ile Gly Pro 340 345 350 Tyr Gly Pro Gly Val Ser Ala Ala Ala Ala Ala Gly Val Tyr Leu Ile 355 360 365 Gly Pro Gly Leu Ile Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly 370 375 380 Leu Ile Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly 385 390 395 400 Pro Gly Val Tyr Gly Pro Gly Leu Ile Gly Pro Ser Ala Ser Ala Ala 405 410 415 Ala Ala Ala Gly Val Tyr Gly Ser Gly Pro Gly Val Tyr Gly Pro Tyr 420 425 430 Gly Pro Gly Val Ser Gly Pro Gly Ser Gly Leu Ile Gly Val Gly Pro 435 440 445 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Val Tyr Gly Pro 450 455 460 Gly Leu Ile Gly Pro Tyr Gly Pro Gly Val Ser Ala Ala Ala Ala Ala 465 470 475 480 Gly Pro Gly Ser Gly Val Tyr Gly Pro Gly Ala Ser Gly Val Asn Gly 485 490 495 Pro Gly Ser Gly Val Tyr Gly Pro Gly Leu Ile Gly Pro Gly Val Ser 500 505 510 Ala Ala Ala Ala Ala Gly Val Tyr Leu Ile Gly Pro Gly Leu Ile Gly 515 520 525 Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Val Tyr Gly 530 535 540 Ser Gly Pro Gly Leu Ile Gly Pro Tyr Gly Pro Gly Val Ser Gly Ser 545 550 555 560 Gly Leu Ile Gly Pro Gly Leu Ile Gly Pro Tyr Ala Ser Ala Ala Ala 565 570 575 Ala Ala Gly Pro Gly Ser Gly Leu Ile Gly Pro Gly Ala Ser 580 585 590 <210> 42 <211> 587 <212> PRT <213> Synthetic sequence <220> <223> Met-PRT1028 <400> 42 Met Gly Pro Gly Ile Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala 1 5 10 15 Ala Ala Ala Gly Thr Gly Pro Gly Ser Gly Ile Phe Gly Pro Gly Thr 20 25 30 Ser Gly Thr Tyr Gly Pro Gly Ile Phe Gly Pro Gly Ile Phe Gly Pro 35 40 45 Gly Ser Ser Ala Ala Ala Ala Ala Gly Pro Gly Thr Tyr Gly Pro Gly 50 55 60 Ile Phe Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser 65 70 75 80 Gly Ile Phe Gly Pro Gly Ala Ser Gly Thr Tyr Gly Pro Gly Ile Phe 85 90 95 Gly Pro Gly Ile Phe Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly 100 105 110 Thr Tyr Gly Ser Gly Pro Gly Ile Phe Gly Pro Tyr Gly Ser Ala Ala 115 120 125 Ala Ala Ala Gly Pro Gly Ser Gly Thr Tyr Gly Thr Gly Pro Tyr Gly 130 135 140 Pro Gly Ala Ser Gly Pro Gly Thr Tyr Gly Pro Gly Ile Phe Gly Pro 145 150 155 160 Ser Ala Ser Ala Ala Ala Ala Ala Gly Ser Gly Ile Phe Gly Pro Gly 165 170 175 Thr Tyr Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Thr Tyr Gly 180 185 190 Ser Gly Pro Gly Ile Phe Gly Pro Tyr Gly Pro Gly Thr Ser Gly Ser 195 200 205 Gly Ile Phe Gly Pro Gly Ile Phe Gly Pro Tyr Ala Ser Ala Ala Ala 210 215 220 Ala Ala Gly Pro Gly Ile Phe Gly Pro Tyr Gly Pro Gly Ser Ser Ala 225 230 235 240 Ala Ala Ala Ala Gly Thr Tyr Gly Tyr Gly Pro Gly Ile Phe Gly Pro 245 250 255 Tyr Gly Pro Gly Ala Ser Gly Thr Gly Pro Gly Ser Gly Thr Tyr Gly 260 265 270 Pro Gly Ile Phe Gly Pro Gly Thr Ser Ala Ala Ala Ala Ala Gly Pro 275 280 285 Gly Ile Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala 290 295 300 Gly Thr Tyr Gly Pro Gly Ile Phe Gly Pro Gly Thr Tyr Gly Pro Gly 305 310 315 320 Ser Ser Gly Pro Gly Ile Phe Gly Pro Tyr Gly Pro Gly Ser Ser Ala 325 330 335 Ala Ala Ala Ala Gly Thr Tyr Gly Pro Gly Ile Phe Gly Pro Tyr Gly 340 345 350 Pro Gly Thr Ser Ala Ala Ala Ala Ala Gly Thr Tyr Ile Phe Gly Pro 355 360 365 Gly Ile Phe Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Ile Phe 370 375 380 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 385 390 395 400 Thr Tyr Gly Pro Gly Ile Phe Gly Pro Ser Ala Ser Ala Ala Ala Ala 405 410 415 Ala Gly Thr Tyr Gly Ser Gly Pro Gly Thr Tyr Gly Pro Tyr Gly Pro 420 425 430 Gly Thr Ser Gly Pro Gly Ser Gly Ile Phe Gly Thr Gly Pro Tyr Gly 435 440 445 Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Thr Tyr Gly Pro Gly Ile 450 455 460 Phe Gly Pro Tyr Gly Pro Gly Thr Ser Ala Ala Ala Ala Ala Gly Pro 465 470 475 480 Gly Ser Gly Thr Tyr Gly Pro Gly Ala Ser Gly Thr Gly Pro Gly Ser 485 490 495 Gly Thr Tyr Gly Pro Gly Ile Phe Gly Pro Gly Thr Ser Ala Ala Ala 500 505 510 Ala Ala Gly Thr Tyr Ile Phe Gly Pro Gly Ile Phe Gly Pro Tyr Gly 515 520 525 Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Thr Tyr Gly Ser Gly Pro 530 535 540 Gly Ile Phe Gly Pro Tyr Gly Pro Gly Thr Ser Gly Ser Gly Ile Phe 545 550 555 560 Gly Pro Gly Ile Phe Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly 565 570 575 Pro Gly Ser Gly Ile Phe Gly Pro Gly Ala Ser 580 585 <210> 43 <211> 601 <212> PRT <213> Artificial sequence <220> <223> PRT917 <400> 43 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Leu 1 5 10 15 Ile Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Val 20 25 30 Asn Gly Pro Gly Ser Gly Leu Ile Gly Pro Gly Val Ser Gly Val Tyr 35 40 45 Gly Pro Gly Leu Ile Gly Pro Gly Leu Ile Gly Pro Gly Ser Ser Ala 50 55 60 Ala Ala Ala Ala Gly Pro Gly Val Tyr Gly Pro Gly Leu Ile Gly Pro 65 70 75 80 Ser Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Leu Ile Gly 85 90 95 Pro Gly Ala Ser Gly Val Tyr Gly Pro Gly Leu Ile Gly Pro Gly Leu 100 105 110 Ile Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Val Tyr Gly Ser 115 120 125 Gly Pro Gly Leu Ile Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly 130 135 140 Pro Gly Ser Gly Val Tyr Gly Val Gly Pro Tyr Gly Pro Gly Ala Ser 145 150 155 160 Gly Pro Gly Val Tyr Gly Pro Gly Leu Ile Gly Pro Ser Ala Ser Ala 165 170 175 Ala Ala Ala Ala Gly Ser Gly Leu Ile Gly Pro Gly Val Tyr Gly Pro 180 185 190 Tyr Ala Ser Ala Ala Ala Ala Ala Gly Val Tyr Gly Ser Gly Pro Gly 195 200 205 Leu Ile Gly Pro Tyr Gly Pro Gly Val Ser Gly Ser Gly Leu Ile Gly 210 215 220 Pro Gly Leu Ile Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro 225 230 235 240 Gly Leu Ile Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala 245 250 255 Gly Val Tyr Gly Tyr Gly Pro Gly Leu Ile Gly Pro Tyr Gly Pro Gly 260 265 270 Ala Ser Gly Val Asn Gly Pro Gly Ser Gly Val Tyr Gly Pro Gly Leu 275 280 285 Ile Gly Pro Gly Val Ser Ala Ala Ala Ala Ala Gly Pro Gly Leu Ile 290 295 300 Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Val Tyr 305 310 315 320 Gly Pro Gly Leu Ile Gly Pro Gly Val Tyr Gly Pro Gly Ser Ser Gly 325 330 335 Pro Gly Leu Ile Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala 340 345 350 Ala Gly Val Tyr Gly Pro Gly Leu Ile Gly Pro Tyr Gly Pro Gly Val 355 360 365 Ser Ala Ala Ala Ala Ala Gly Val Tyr Leu Ile Gly Pro Gly Leu Ile 370 375 380 Gly Pro Tyr Gly Pro Gly Ala Ser Gly Pro Gly Leu Ile Gly Pro Tyr 385 390 395 400 Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Val Tyr Gly 405 410 415 Pro Gly Leu Ile Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Val 420 425 430 Tyr Gly Ser Gly Pro Gly Val Tyr Gly Pro Tyr Gly Pro Gly Val Ser 435 440 445 Gly Pro Gly Ser Gly Leu Ile Gly Val Gly Pro Tyr Gly Pro Gly Ala 450 455 460 Ser Ala Ala Ala Ala Ala Gly Val Tyr Gly Pro Gly Leu Ile Gly Pro 465 470 475 480 Tyr Gly Pro Gly Val Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly 485 490 495 Val Tyr Gly Pro Gly Ala Ser Gly Val Asn Gly Pro Gly Ser Gly Val 500 505 510 Tyr Gly Pro Gly Leu Ile Gly Pro Gly Val Ser Ala Ala Ala Ala Ala 515 520 525 Gly Val Tyr Leu Ile Gly Pro Gly Leu Ile Gly Pro Tyr Gly Pro Gly 530 535 540 Ala Ser Ala Ala Ala Ala Ala Gly Val Tyr Gly Ser Gly Pro Gly Leu 545 550 555 560 Ile Gly Pro Tyr Gly Pro Gly Val Ser Gly Ser Gly Leu Ile Gly Pro 565 570 575 Gly Leu Ile Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 580 585 590 Ser Gly Leu Ile Gly Pro Gly Ala Ser 595 600 <210> 44 <211> 598 <212> PRT <213> Artificial Sequence <220> <223> PRT1028 <400> 44 Met His His His His His His Ser Ser Gly Ser Ser Gly Pro Gly Ile 1 5 10 15 Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Thr 20 25 30 Gly Pro Gly Ser Gly Ile Phe Gly Pro Gly Thr Ser Gly Thr Tyr Gly 35 40 45 Pro Gly Ile Phe Gly Pro Gly Ile Phe Gly Pro Gly Ser Ser Ala Ala 50 55 60 Ala Ala Ala Gly Pro Gly Thr Tyr Gly Pro Gly Ile Phe Gly Pro Ser 65 70 75 80 Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Ile Phe Gly Pro 85 90 95 Gly Ala Ser Gly Thr Tyr Gly Pro Gly Ile Phe Gly Pro Gly Ile Phe 100 105 110 Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly Thr Tyr Gly Ser Gly 115 120 125 Pro Gly Ile Phe Gly Pro Tyr Gly Ser Ala Ala Ala Ala Ala Gly Pro 130 135 140 Gly Ser Gly Thr Tyr Gly Thr Gly Pro Tyr Gly Pro Gly Ala Ser Gly 145 150 155 160 Pro Gly Thr Tyr Gly Pro Gly Ile Phe Gly Pro Ser Ala Ser Ala Ala 165 170 175 Ala Ala Ala Gly Ser Gly Ile Phe Gly Pro Gly Thr Tyr Gly Pro Tyr 180 185 190 Ala Ser Ala Ala Ala Ala Ala Gly Thr Tyr Gly Ser Gly Pro Gly Ile 195 200 205 Phe Gly Pro Tyr Gly Pro Gly Thr Ser Gly Ser Gly Ile Phe Gly Pro 210 215 220 Gly Ile Phe Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly 225 230 235 240 Ile Phe Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly 245 250 255 Thr Tyr Gly Tyr Gly Pro Gly Ile Phe Gly Pro Tyr Gly Pro Gly Ala 260 265 270 Ser Gly Thr Gly Pro Gly Ser Gly Thr Tyr Gly Pro Gly Ile Phe Gly 275 280 285 Pro Gly Thr Ser Ala Ala Ala Ala Ala Gly Pro Gly Ile Phe Gly Pro 290 295 300 Tyr Gly Pro Gly Ala Ser Ala Ala Ala Ala Ala Gly Thr Tyr Gly Pro 305 310 315 320 Gly Ile Phe Gly Pro Gly Thr Tyr Gly Pro Gly Ser Ser Gly Pro Gly 325 330 335 Ile Phe Gly Pro Tyr Gly Pro Gly Ser Ser Ala Ala Ala Ala Ala Gly 340 345 350 Thr Tyr Gly Pro Gly Ile Phe Gly Pro Tyr Gly Pro Gly Thr Ser Ala 355 360 365 Ala Ala Ala Ala Gly Thr Tyr Ile Phe Gly Pro Gly Ile Phe Gly Pro 370 375 380 Tyr Gly Pro Gly Ala Ser Gly Pro Gly Ile Phe Gly Pro Tyr Gly Pro 385 390 395 400 Gly Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Thr Tyr Gly Pro Gly 405 410 415 Ile Phe Gly Pro Ser Ala Ser Ala Ala Ala Ala Ala Gly Thr Tyr Gly 420 425 430 Ser Gly Pro Gly Thr Tyr Gly Pro Tyr Gly Pro Gly Thr Ser Gly Pro 435 440 445 Gly Ser Gly Ile Phe Gly Thr Gly Pro Tyr Gly Pro Gly Ala Ser Ala 450 455 460 Ala Ala Ala Ala Gly Thr Tyr Gly Pro Gly Ile Phe Gly Pro Tyr Gly 465 470 475 480 Pro Gly Thr Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Thr Tyr 485 490 495 Gly Pro Gly Ala Ser Gly Thr Gly Pro Gly Ser Gly Thr Tyr Gly Pro 500 505 510 Gly Ile Phe Gly Pro Gly Thr Ser Ala Ala Ala Ala Ala Gly Thr Tyr 515 520 525 Ile Phe Gly Pro Gly Ile Phe Gly Pro Tyr Gly Pro Gly Ala Ser Ala 530 535 540 Ala Ala Ala Ala Gly Thr Tyr Gly Ser Gly Pro Gly Ile Phe Gly Pro 545 550 555 560 Tyr Gly Pro Gly Thr Ser Gly Ser Gly Ile Phe Gly Pro Gly Ile Phe 565 570 575 Gly Pro Tyr Ala Ser Ala Ala Ala Ala Ala Gly Pro Gly Ser Gly Ile 580 585 590 Phe Gly Pro Gly Ala Ser 595

Claims

1. A method for preparing a protein molded body, comprising the step of hydrolyzing the ester group by bringing the raw material molded body containing a protein with esterified hydroxyl groups into contact with an acidic or alkaline medium under a tensile force applied thereto, wherein the tensile force is a tensile force that causes a rate of change in the size of the raw material molded body before and after contact with the medium of 87 to 113%.

2. The method for preparing a protein shaped body according to claim 1, wherein: The medium is an aqueous solution.

3. The method for preparing a protein shaped body according to claim 2, wherein: The aqueous solution is an alkaline aqueous solution with a pH value less than 12.

4. The method for producing a protein shaped body according to claim 2 or 3, wherein: The tensile force is such a magnitude that the raw material molded body does not shrink due to contact with the aqueous solution.

5. The method for producing a protein shaped body according to any one of claims 1 to 3, wherein: The protein is a structural protein.

6. The method for preparing a protein shaped body according to claim 5, wherein: The structural protein is fibroin.

7. The method for preparing a protein shaped body according to claim 6, wherein: The fibroin is spider silk fibroin.

8. The method for producing a protein shaped body according to any one of claims 1 to 3, wherein: The protein whose hydroxyl groups are esterified contains formate.

9. The method for producing a protein shaped body according to any one of claims 1 to 3, wherein: The raw material molded body is at least one selected from fibers, heated and pressed molded bodies, films, porous bodies, gels, and resins.

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