Modified transglutaminase

Abstract

An object of the present invention is to find a new mutation effective for improving transglutaminase, and to provide a highly useful modified transglutaminase. Disclosed is a highly useful modified transglutaminase having an amino acid substitution that results in a reduction in temperature stability, an improvement in heat resistance, an improvement in oxidation resistance, an improvement in reactivity, or conversion into deamidase.

1 . A modified transglutaminase having an amino acid sequence which comprises any one of the following amino acid substitutions (1) to (134) in the sequence of SEQ ID NO: 1 or an amino acid sequence showing 80% or more identity to the amino acid sequence (provided that a difference in amino acid sequence occurs at a portion other than the position of the amino acid substitution), the modified transglutaminase exhibiting a property change corresponding to the amino acid substitution:
 (1) an amino acid substitution in which the mutation point is V6, the amino acid after substitution is Q, I, M, S, C, K, L, H, F, G, N, P, R, W or Y, and the property change due to the amino acid substitution is a reduction in temperature stability;   (2) an amino acid substitution in which the mutation point is R26, the amino acid after substitution is K, Q, M, H, Y, D, G, N, P or S, and the property change due to the amino acid substitution is a reduction in temperature stability;   (3) an amino acid substitution in which the mutation point is E28, the amino acid after substitution is V, Q, W, R, K, M, N, F, G, L, P or Y, and the property change due to the amino acid substitution is a reduction in temperature stability;   (4) an amino acid substitution in which the mutation point is V30, the amino acid after substitution is P, C, A, E, F, G, H, K, N, Q, R, W, Y or L, and the property change due to the amino acid substitution is a reduction in temperature stability;   (5) an amino acid substitution in which the mutation point is Y34, the amino acid after substitution is A, and the property change due to the amino acid substitution is a reduction in temperature stability;   (6) an amino acid substitution in which the mutation point is Y42, the amino acid after substitution is F, A, C, D, E, G, I, L, M, Q, S, T, V or W, and the property change due to the amino acid substitution is a reduction in temperature stability;   (7) an amino acid substitution in which the mutation point is E58, the amino acid after substitution is Y, M, A, F, I, V, R, K, N, L, S, Q, G or H, and the property change due to the amino acid substitution is a reduction in temperature stability;   (8) an amino acid substitution in which the mutation point is W59, the amino acid after substitution is R, N, Y, A, S, I, V, D, G or P, and the property change due to the amino acid substitution is a reduction in temperature stability;   (9) an amino acid substitution in which the mutation point is L60, the amino acid after substitution is I, M, V, A, C, E, F, Q, S, T, W or Y, and the property change due to the amino acid substitution is a reduction in temperature stability;   (10) an amino acid substitution in which the mutation point is Y62, the amino acid after substitution is C, R, G, K or S, and the property change due to the amino acid substitution is a reduction in the temperature stability;   (11) an amino acid substitution in which the mutation point is V65, the amino acid after substitution is N, L, M, F, W or Y, and the property change due to the amino acid substitution is a reduction in temperature stability;   (12) an amino acid substitution in which the mutation point is V67, the amino acid after substitution is L, N, A, C, M, Q or S, and the property change due to the amino acid substitution is a reduction in the temperature stability;   (13) an amino acid substitution in which the mutation point is T68, the amino acid after substitution is C, L, A, S, M, F, N, Q or Y, and the property change due to the amino acid substitution is a reduction in temperature stability;   (14) an amino acid substitution in which the mutation point is W69, the amino acid after substitution is H, M, I, C, E, F, G, K, L, N, Q, R, S, T or V, and the property change due to the amino acid substitution is a reduction in temperature stability;   (15) an amino acid substitution in which the mutation point is Q74, the amino acid after substitution is W, D, G or K, and the property change due to the amino acid substitution is a reduction in temperature stability;   (16) an amino acid substitution in which the mutation point is Y75, the amino acid after substitution is R, Q, T or G, and the property change due to the amino acid substitution is a reduction in temperature stability;   (17) an amino acid substitution in which the mutation point is T77, the amino acid after substitution is M, H, E, C or G, and the property change due to the amino acid substitution is a reduction in temperature stability;   (18) an amino acid substitution in which the mutation point is F85, the amino acid after substitution is M, and the property change due to the amino acid substitution is a reduction in temperature stability;   (19) an amino acid substitution in which the mutation point is F90, the amino acid after substitution is C, M, H, L or V, and the property change due to the amino acid substitution is a reduction in temperature stability;   (20) an amino acid substitution in which the mutation point is F108, the amino acid after substitution is R, L, T, A, I, K, N or V, and the property change due to the amino acid substitution is a reduction in temperature stability;   (21) an amino acid substitution in which the mutation point is F117, the amino acid after substitution is M or L, and the property change due to the amino acid substitution is a reduction in temperature stability;   (22) an amino acid substitution in which the mutation point is S199, the amino acid after substitution is G, M, N, K or V, and the property change due to the amino acid substitution is a reduction in temperature stability;   (23) an amino acid substitution in which the mutation point is F202, the amino acid after substitution is L or W, and the property change due to the amino acid substitution is a reduction in temperature stability;   (24) an amino acid substitution in which the mutation point is W203, the amino acid after substitution is F, and the property change due to the amino acid substitution is a reduction in temperature stability;   (25) an amino acid substitution in which the mutation point is F254, the amino acid after substitution is Y or M, and the property change due to the amino acid substitution is a reduction in temperature stability;   (26) an amino acid substitution in which the mutation point is T273, and the amino acid after substitution is I, V, M, C, S, L, R, G, A, E, F, Y, D, K, W or H, and the property change due to the amino acid substitution is a reduction in temperature stability;   (27) an amino acid substitution in which the mutation point is N276, the amino acid after substitution is C, E, K, L, S, T or V, and the property change due to the amino acid substitution is a reduction in temperature stability;   (28) an amino acid substitution in which the mutation point is Y278, the amino acid after substitution is M, L, H, I, K, R, W, C, G, N, Q, S, T or V, and the property change due to the amino acid substitution is a reduction in temperature stability;   (29) an amino acid substitution in which the mutation point is S284, the amino acid after substitution is W, Y, M, F or N, and the property change due to the amino acid substitution is a reduction in temperature stability;   (30) an amino acid substitution in which the mutation point is Y291, the amino acid after substitution is I, W, L, A, C, K, N, Q, R, S or V, and the property change due to the amino acid substitution is a reduction in temperature stability;   (31) an amino acid substitution in which the mutation point is S299, the amino acid after substitution is I, Y, V, K, M, Q, A, F, G or E, and the property change due to the amino acid substitution is a reduction in temperature stability;   (32) an amino acid substitution in which the mutation point is S303, the amino acid after substitution is N, G, C, V, P or Y, and the property change due to the amino acid substitution is a reduction in temperature stability;   (33) an amino acid substitution in which the mutation point is Y310, the amino acid after substitution is C, M or I, and the property change due to the amino acid substitution is a reduction in temperature stability;   (34) an amino acid substitution in which the mutation point is D3, the amino acid after substitution is Q, P, E, S or Y, and the property change due to the amino acid substitution is an improvement in heat resistance;   (35) an amino acid substitution in which the mutation point is R26, the amino acid after substitution is V, and the property change due to the amino acid substitution is an improvement in heat resistance;   (36) an amino acid substitution in which the mutation point is Y34, the amino acid after substitution is W, and the property change due to the amino acid substitution is an improvement in heat resistance;   (37) an amino acid substitution in which the mutation point is V67, the amino acid after substitution is H, and the property change due to the amino acid substitution is an improvement in heat resistance;   (38) an amino acid substitution in which the mutation point is T68, the amino acid after substitution is V or I, and the property change due to the amino acid substitution is an improvement in heat resistance;   (39) an amino acid substitution in which the mutation point is Q74, the amino acid after substitution is F, and the property change due to the amino acid substitution is an improvement in heat resistance;   (40) an amino acid substitution in which the mutation point is T77, the amino acid after substitution is Q, and the property change due to the amino acid substitution is an improvement in heat resistance;   (41) an amino acid substitution in which the mutation point is S199, the amino acid after substitution is C or Q, and the property change due to the amino acid substitution is an improvement in heat resistance;   (42) an amino acid substitution in which the mutation point is T273, the amino acid after substitution is Q, and the property change due to the amino acid substitution is an improvement in heat resistance;   (43) an amino acid substitution in which the mutation point is S284, the amino acid after substitution is L, H, K, P or R, and the property change due to the amino acid substitution is an improvement in heat resistance;   (44) an amino acid substitution in which the mutation point is S299, the amino acid after substitution is N, and the property change due to the amino acid substitution is an improvement in heat resistance;   (45) an amino acid substitution in which the mutation point is S303, the amino acid after substitution is K, and the property change due to the amino acid substitution is an improvement in heat resistance;   (46) an amino acid substitution in which the mutation point is D3, the amino acid after substitution is E, Q, S or Y, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (47) an amino acid substitution in which the mutation point is V6, the amino acid after substitution is P, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (48) an amino acid substitution in which the mutation point is R26, the amino acid after substitution is M, K, W, C, Q, G, Y, E, T, N, D, I, S, P or V, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (49) an amino acid substitution in which the mutation point is E28, the amino acid after substitution is L, M, K, C, V, R, W, G, N, F, Y or H, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (50) an amino acid substitution in which the mutation point is Y42, the amino acid after substitution is L, N or F, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (51) an amino acid substitution in which the mutation point is E58, the amino acid after substitution is Q, A, I, V, L, T, M, K, Y, W, F or R, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (52) an amino acid substitution in which the mutation point is V67, the amino acid after substitution is T, S or A, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (53) an amino acid substitution in which the mutation point is T68, the amino acid after substitution is L, I, V or M, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (54) an amino acid substitution in which the mutation point is Q74, the amino acid after substitution is V, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (55) an amino acid substitution in which the mutation point is T77, the amino acid after substitution is D, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (56) an amino acid substitution in which the mutation point is S199, the amino acid after substitution is C, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (57) an amino acid substitution in which the mutation point is T273, the amino acid after substitution is E, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (58) an amino acid substitution in which the mutation point is S284, the amino acid after substitution is R or H, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (59) an amino acid substitution in which the mutation point is Y291, the amino acid after substitution is I, S, F, L, C, N, V or M, and the property change due to the amino acid substitution is an improvement in oxidation resistance;   (60) an amino acid substitution in which the mutation point is S284, the amino acid after substitution is M, K or V, and the property change due to the amino acid substitution is an improvement in reactivity;   (61) an amino acid substitution in which the mutation point is F251, the amino acid after substitution is Y, and the property change due to the amino acid substitution is an improvement in reactivity;   (62) an amino acid substitution in which the mutation points are V6 and Y75, the amino acid after substitution at the mutation point V6 is E, the amino acid after substitution at the mutation point Y75 is F, and the property change due to the amino acid substitution is an improvement in reactivity;   (63) an amino acid substitution in which the mutation points are D3 and T77, the amino acid after substitution at the mutation point D3 is P, the amino acid after substitution at the mutation point T77 is Q, and the property change due to the amino acid substitution is an improvement in reactivity;   (64) an amino acid substitution in which the mutation point is D3, the amino acid after substitution is Q, S or Y, and the property changes due to the amino acid substitution are improvements in heat resistance and oxidation resistance;   (65) an amino acid substitution in which the mutation point is D3, the amino acid after substitution is P, and the property changes due to the amino acid substitution are improvements in heat resistance and reactivity;   (66) an amino acid substitution in which the mutation point is D3, the amino acid after substitution is E, and the property changes due to the amino acid substitution are improvements in heat resistance, oxidation resistance and reactivity;   (67) an amino acid substitution in which the mutation point is V6, the amino acid after substitution is P, and the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in oxidation resistance;   (68) an amino acid substitution in which the mutation point is R26, the amino acid after substitution is K, Q, M, Y, D, G, N, P or S, and the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in oxidation resistance;   (69) an amino acid substitution in which the mutation point is R26, the amino acid after substitution is V, and the property changes due to the amino acid substitution are improvements in heat resistance and oxidation resistance;   (70) an amino acid substitution in which the mutation point is R26, the amino acid after substitution is H, and the property changes due to the amino acid substitution are a reduction in temperature stability, and improvements in oxidation resistance and reactivity;   (71) an amino acid substitution in which the mutation point is E28, the amino acid after substitution is V, R, K, M, N, F, G, L or Y, and the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in oxidation resistance;   (72) an amino acid substitution in which the mutation point is V30, the amino acid after substitution is P, G, N, R or Y, and the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in reactivity;   (73) an amino acid substitution in which the mutation point is Y42, the amino acid after substitution is F, L or M, and the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in oxidation resistance;   (74) an amino acid substitution in which the mutation point is E58, the amino acid after substitution is Y, M, A, F, I, V, R, K, L or Q, and the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in oxidation resistance;   (75) an amino acid substitution in which the mutation point is L60, the amino acid after substitution is I, and the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in reactivity;   (76) an amino acid substitution in which the mutation point is V67, the amino acid after substitution is A or S, and the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in oxidation resistance;   (77) an amino acid substitution in which the mutation point is T68, the amino acid after substitution is C, L or M, and the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in oxidation resistance;   (78) an amino acid substitution in which the mutation point is T68, the amino acid after substitution is V or I, and the property changes due to the amino acid substitution are improvements in heat resistance and oxidation resistance;   (79) an amino acid substitution in which the mutation point is Q74, the amino acid after substitution is V, and the property changes due to the amino acid substitution are improvements in oxidation resistance and reactivity;   (80) an amino acid in which the mutation point is T77, the amino acid after substitution is C, and the property changes due to the amino acid substitution are a reduction in temperature stability and improvement in oxidation resistance;   (81) an amino acid in which the mutation point is T77, the amino acid after substitution is E, the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in reactivity;   (82) an amino acid in which the mutation point is T77, the amino acid after substitution is D, and the property changes due to the amino acid are improvements in oxidation resistance and reactivity;   (83) an amino acid in which the mutation point is S199, the amino acid after substitution is G, and the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in reactivity;   (84) an amino acid in which the mutation point is S199, the amino acid after substitution is C, and the property changes due to the amino acid substitution are improvements in heat resistance, oxidation resistance and reactivity;   (85) an amino acid in which the mutation point is T273, the amino acid after substitution is E, the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in oxidation resistance;   (86) an amino acid in which the mutation point is S284, the amino acid after substitution is M or F, the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in reactivity;   (87) an amino acid in which the mutation point is S284, the amino acid after substitution is L or K, and the property changes due to the amino acid substitution are improvements in heat resistance and reactivity;   (88) an amino acid in which the mutation point is S284, the amino acid after substitution is H or R, and the property changes due to the amino acid substitution are improvements in heat resistance and oxidation resistance;   (89) an amino acid in which the mutation point is Y291, the amino acid after substitution is I, L, C, N, S or V, the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in oxidation resistance;   (90) an amino acid in which the mutation point is S299, the amino acid after substitution is V, K, M or A, the property changes due to the amino acid substitution are a reduction in temperature stability and an improvement in reactivity;   (91) an amino acid in which the mutation point is S303, the amino acid after substitution is K, and the property changes due to the amino acid substitution are improvements in heat resistance and reactivity;   (92) an amino acid in which the mutation point is R5, the amino acid after substitution is Q, P, C, M, I, V, Y, F, S, N, T or G, and the property change due to amino acid substitution is conversion into deamidase;   (93) an amino acid in which the mutation point is Y34, the amino acid after substitution is H or M, and the property change due to the amino acid substitution is conversion into deamidase;   (94) an amino acid in which the mutation point is W59, the amino acid after substitution is K or E, and the property change due to the amino acid substitution is conversion into deamidase;   (95) an amino acid in which the mutation point is S61, the amino acid after substitution is T, V, Y, D, I, L, N, E, M, F, W, Q, P, H or K, and the property change due to the amino acid substitution is conversion into deamidase;   (96) an amino acid in which the mutation point is Y62, the amino acid after substitution is D or P, and the property change due to the amino acid substitution is conversion into deamidase;   (97) an amino acid in which the mutation point is G63, the amino acid after substitution is D, Q, Y, R, K, H, P, M, N, C, F, L, W, T, V or S, the property change due to amino acid substitution is conversion into deamidase;   (98) an amino acid in which the mutation point is V65, the amino acid after substitution is C, T or K, and the property change due to the amino acid substitution is conversion into deamidase;   (99) an amino acid in which the mutation point is G66, the amino acid after substitution is W or K, and the property change due to the amino acid substitution is conversion into deamidase;   (100) an amino acid in which the mutation point is T68, the amino acid after substitution is P or H, and the property change due to the amino acid substitution is conversion into deamidase;   (101) an amino acid in which the mutation point is W69, the amino acid after substitution is Y, D or P, and the property change due to the amino acid substitution is conversion into deamidase;   (102) an amino acid in which the mutation point is Q74, the amino acid after substitution is R or P, and the property change due to the amino acid substitution is conversion into deamidase;   (103) an amino acid in which the mutation point is F85, the amino acid after substitution is Y, W, L, I, Q, C, T, A, V, S, R, H or N, the property change due to amino acid substitution is conversion into deamidase;   (104) an amino acid in which the mutation point is F108, the amino acid after substitution is Q, C, E, S or N, the property change due to amino acid substitution is conversion into deamidase;   (105) an amino acid in which the mutation point is F117, the amino acid after substitution is C, I, W, V, A, G, T or N, and the property change due to the amino acid substitution is conversion into deamidase;   (106) an amino acid in which the mutation point is Y198, the amino acid after substitution is F, H, L, S, M or I, the property change due to the amino acid substitution is conversion into deamidase;   (107) an amino acid in which the mutation point is S199, the amino acid after substitution is Q or P, and the property change due to the amino acid substitution is conversion into deamidase;   (108) an amino acid in which the mutation point is K200, the amino acid after substitution is Y, M, I, R, L or V, and the property change due to the amino acid substitution is conversion into deamidase;   (109) an amino acid in which the mutation point is H201, the amino acid after substitution is K, R, M, L or Q, and the property change due to the amino acid substitution is conversion into deamidase;   (110) an amino acid in which the mutation point is F202, the amino acid after substitution is Y, M, H, V or C, the property change due to amino acid substitution is conversion into deamidase;   (111) an amino acid in which the mutation point is W203, the amino acid after substitution is Y, and the property change due to the amino acid substitution is conversion into deamidase;   (112) an amino acid in which the mutation point is F223, the amino acid after substitution is Y, M, L, W, V, H, G or A, the property change due to the amino acid substitution is conversion into deamidase;   (113) an amino acid in which the mutation point is R238, the amino acid after substitution is A, D, V, G, H or S, the property change due to amino acid substitution is deamidation;   (114) an amino acid in which the mutation point is F251, the amino acid after substitution is H, N, C, M, R, S, A, T, L, P, G, V or Q, the property change due to amino acid substitution is conversion into deamidase;   (115) an amino acid in which the mutation point is V252, the amino acid after substitution is M, L, T or C, the property change due to the amino acid substitution is conversion into deamidase;   (116) an amino acid in which the mutation point is N253, the amino acid after substitution is T, V, K, C or R, the property change due to amino acid substitution is conversion into deamidase;   (117) an amino acid in which the mutation point is Y256, the amino acid after substitution is L, V or I, and the property change due to the amino acid substitution is conversion into deamidase;   (118) an amino acid in which the mutation point is G257, the amino acid after substitution is A or C, and the property change due to the amino acid substitution is conversion into deamidase;   (119) an amino acid in which the mutation point is W258, the amino acid after substitution is Y, F or N, and the property change due to the amino acid substitution is conversion into deamidase;   (120) an amino acid in which the mutation point is T273, the amino acid after substitution is N, and the property change due to the amino acid substitution is conversion into deamidase;   (121) an amino acid in which the mutation point is G275, amino acid after substitution is A, C, S, V, K, I, F, H, R, L, P, Q, Y, N, M or T, and the property change by amino acid substitution is conversion into deamidase;   (122) an amino acid in which the mutation point is N276, the amino acid after substitution is G, M, Q or H, and the property change due to the amino acid substitution is conversion into deamidase;   (123) an amino acid in which the mutation point is H277, the amino acid after substitution is N, S, Q, C, E, K, D, I, R, M, P, L, W, V, Y, G, F or T, and the property change due to the amino acid substitution is conversion into deamidase;   (124) an amino acid in which the mutation point is Y278, the amino acid after substitution is P or D, and the property change due to the amino acid substitution is conversion into deamidase;   (125) an amino acid in which the mutation point is H279, the amino acid after substitution is N, and the property change due to the amino acid substitution is conversion into deamidase;   (126) an amino acid in which the mutation point is S284, the amino acid after substitution is C, and the property change due to the amino acid substitution is conversion into deamidase;   (127) an amino acid in which the mutation point is M288, the amino acid after substitution is V, Q or T, and the property change due to the amino acid substitution is conversion into deamidase;   (128) an amino acid in which the mutation point is V290, the amino acid after substitution is T, C, L, M, A, S or N, and the property change due to the amino acid substitution is conversion into deamidase;   (129) an amino acid in which the mutation point is Y291, the amino acid after substitution is H, T, E or G, and the property change due to the amino acid substitution is conversion into deamidase;   (130) an amino acid in which the mutation point is W298, the amino acid after substitution is F, Y, I, L or M, and the property change due to the amino acid substitution is conversion into deamidase;   (131) an amino acid in which the mutation point is S299, the amino acid after substitution is N or P, and the property change due to the amino acid substitution is conversion into deamidase;   (132) an amino acid in which the mutation point is Y302, the amino acid after substitution is L, H, M, V, C, T, P, S or W, the property change due to amino acid substitution is conversion into deamidase;   (133) an amino acid in which the mutation point is S303, the amino acid after substitution is I, Q, D, H or E, and the property change due to the amino acid substitution is conversion into deamidase; and   (134) an amino acid in which the mutation point is F305, the amino acid after substitution is W, H or Y, and the property change due to the amino acid substitution is conversion into deamidase.   
     
     
         2 . The modified transglutaminase according to  claim 1 , wherein the identity is 82% or more. 
     
     
         3 . The modified transglutaminase according to  claim 1 , wherein the identity is 85% or more. 
     
     
         4 . The modified transglutaminase according to  claim 1 , wherein the identity is 90% or more. 
     
     
         5 . The modified transglutaminase according to  claim 1 , comprising an amino acid sequence of any of SEQ ID NOs: 2 to 10. 
     
     
         6 . A gene encoding the modified transglutaminase according to  claim 1 . 
     
     
         7 . The gene according to  claim 6 , comprising a base sequence of any of SEQ ID NOs: 18 to 26. 
     
     
         8 . A recombinant DNA comprising the gene according to  claim 6 . 
     
     
         9 . A microorganism possessing the recombinant DNA according to  claim 8 . 
     
     
         10 . An enzyme preparation comprising the modified transglutaminase according to  claim 1 . 
     
     
         11 . A method for preparing a modified transglutaminase, comprising the following steps (I) to (III):
 (I) providing a nucleic acid encoding the amino acid sequence of the modified transglutaminase according to  claim 1 ;   (II) expressing the nucleic acid, and   (III) recovering an expression product.   
     
     
         12 . The method according to  claim 11 , wherein the amino acid sequence is an amino acid sequence of any one of SEQ ID NOs: 2 to 10. 
     
     
         13 . The method according to  claim 12 , wherein the nucleic acid comprises a base sequence of any one of SEQ ID NOs: 18 to 26.