Mutant protein having the peptide-synthesizing activity

Abstract

The present invention aims at providing an excellent peptide-synthesizing protein and a method for efficiently producing a peptide. The peptide is synthesized by reacting an amine component and a carboxy component in the presence of at least one of proteins shown in the following (I) and (II).

Description

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a view showing experimental results for pH stability.

FIG. 2 is a view showing experimental results for optimal reaction temperature.

FIG. 3 is a view showing experimental results for temperature stability.

FIG. 4 is a view showing a tertiary structure of a protein having an amino acid sequence of SEQ ID NO:209.

FIG. 5 is a tertiary structure of a protein having an amino acid sequence of SEQ ID NO:208.

FIG. 6-1 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-2 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-3 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-4 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-5 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-6 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-7 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-8 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-9 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-10 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-11 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-12 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-13 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-14 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-15 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-16 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-17 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-18 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-19 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-20 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-21 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-22 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-23 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-24 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-25 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-26 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-27 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-28 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-29 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-30 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-31 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-32 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-33 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-34 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-35 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-36 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-37 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-38 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-39 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-40 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-41 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-42 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-43 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-44 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-45 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-46 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-47 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-48 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-49 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-50 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-51 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-52 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-53 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-54 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-55 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-56 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-57 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-58 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-59 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-60 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-61 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-62 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-63 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-64 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-65 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-66 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-67 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-68 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-69 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-70 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-71 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-72 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-73 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-74 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-75 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-76 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-77 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-78 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-79 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-80 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-81 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-82 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-83 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-84 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-85 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-86 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-87 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-88 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-89 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-90 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-91 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-92 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-93 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-94 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-95 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-96 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-97 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-98 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-99 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-100 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-101 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-102 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-103 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-104 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-105 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-106 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-107 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-108 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-109 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-110 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-111 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-112 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-113 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-114 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-115 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-116 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-117 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-118 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-119 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-120 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-121 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-122 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-123 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-124 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-125 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-126 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-127 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-128 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-129 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-130 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-131 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-132 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-133 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

FIG. 6-134 is a view showing atomic coordinates in the tertiary structure (three dimensional structure) of the protein having the amino acid sequence of SEQ ID NO:209.

Claims

1. A mutant protein having an amino acid sequence comprising one or more mutations selected from any of the following mutations 1 to 68 in an amino acid sequence of SEQ ID NO:2: mutation 1 F207V, mutation 2 Q441E, mutation 3 K83A, mutation 4 A301V, mutation 5 V257I, mutation 6 A537G, mutation 7 A324V, mutation 8 N607K, mutation 9 D313E, mutation 10 Q229H, mutation 11 M208A, mutation 12 E551K, mutation 13 F207H, mutation 14 T72A, mutation 15 A137S, mutation 16 L439V, mutation 17 G226S, mutation 18 D619E, mutation 19 Y339H, mutation 20 W327G, mutation 21 V184A, mutation 22 V184C, mutation 23 V184G, mutation 24 V184I, mutation 25 V184L, mutation 26 V184M, mutation 27 V184P, mutation 28 V184S, mutation 29 V184T, mutation 30 Q441K, mutation 31 N442K, mutation 32 D203N, mutation 33 D203S, mutation 34 F207A, mutation 35 F207S, mutation 36 Q441N, mutation 37 F207T, mutation 38 F207I, mutation 39 T210K, mutation 40 W187A, mutation 41 S209A, mutation 42 F211A, mutation 43 F211V, mutation 44 V257A, mutation 45 V257G, mutation 46 V257H, mutation 47 V257M, mutation 48 V257N, mutation 49 V257Q, mutation 50 V257S, mutation 51 V257T, mutation 52 V257W, mutation 53 V257Y, mutation 54 K47G, mutation 55 K47E, mutation 56 N442F, mutation 57 N607R, mutation 58 P214T, mutation 59 Q202E, mutation 60 Y494F, mutation 61 R117A, mutation 62 F207G, mutation 63 S209D, mutation 64 S209G, mutation 65 Q441D, mutation 66 R445D, mutation 67 R445F, mutation 68 N442D.

2. A mutant protein having an amino acid sequence comprising one or more mutations selected from any of the following mutations 239 to 290 and 324 to 377 in an amino acid sequence of SEQ ID NO:2: mutation 239 F207V/Q441Emutation 240 F207V/K83Amutation 241 F207V/E551Kmutation 242 K83A/Q441Emutation 243 M208A/E551Kmutation 244 V257I/Q441Emutation 245 V257I/A537Gmutation 246 F207V/S209Amutation 247 K83A/S209Amutation 248 K83A/F207V/Q441Emutation 249 L439V/F207V/Q441Emutation 250 A537G/F207V/Q441Emutation 251 A301V/F207V/Q441Emutation 252 G226S/F207V/Q441Emutation 253 V257I/F207V/Q441Emutation 254 D619E/F207V/Q441Emutation 255 Y339H/F207V/Q441Emutation 256 N607K/F207V/Q441Emutation 257 A324V/F207V/Q441Emutation 258 Q229H/F207V/Q441Emutation 259 W327G/F207V/Q441Emutation 260 A301V/L439V/A537G/N607Kmutation 261 K83A/Q229H/A301V/D313E/A324V/L439V/A537G/N607Kmutation 262 Q229H/V257I/A301V/A324V/Q441E/A537G/N607Kmutation 263 Q229H/A301V/A324V/Q441E/A537G/N607Kmutation 264 Q229H/V257I/A301V/D313E/A324V/Q441E/A537G/N607Kmutation 265 T72A/A137S/A301V/L439V/Q441E/A537G/N607Kmutation 266 T72A/A137S/A301V/Q441E/A537G/N607Kmutation 267 T72A/A137S/Q229H/A301V/A324V/L439V/A537G/N607Kmutation 268 T72A/A137S/Q229H/A301V/A324V/L439V/Q441E/A537G/N607Kmutation 269 T72A/Q229H/V257I/A301V/D313E/A324V/L439V/Q441E/A537G/N607Kmutation 270 T72A/Q229H/V257I/A301V/D313E/A324V/Q441E/A537G/N607Kmutation 271 T72A/A137S/Q229P/A301V/L439V/Q441E/A537G/N607Kmutation 272 T72A/A137S/Q229L/A301V/L439V/Q441E/A537G/N607Kmutation 273 T72A/A137S/Q229G/A301V/L439V/Q441E/A537G/N607Kmutation 274 T72A/Q229I/V257I/A301V/D313E/A324V/L439V/Q441E/A537G/N607Kmutation 275 T72A/A137S/I228G/Q229P/A301V/L439V/Q441E/A537G/N607Kmutation 276 T72A/A137S/I228L/Q229P/A301V/L439V/Q441E/A537G/N607Kmutation 277 T72A/A137S/I228D/Q229P/A301V/L439V/Q441E/A537G/N607Kmutation 278 T72A/A137S/Q229P/I230D/A301V/L439V/Q441E/A537G/N607Kmutation 279 T72A/A137S/Q229P/I230V/A301V/L439V/Q441E/A537G/N607Kmutation 280 T72A/I228S/Q229H/V257I/A301V/D313E/A324V/L439V/Q441E/A537G/N607Kmutation 281 T72A/Q229H/S256C/V257I/A301V/D313E/A324V/L439V/Q441E/A537G/N607Kmutation 282 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607Kmutation 283 T72A/A137S/Q229P/A301V/A324V/L439V/Q441E/A537G/N607Kmutation 284 T72A/Q229P/V257I/A301G/D313E/A324V/Q441E/A537G/N607Kmutation 285 T72A/Q229P/V257I/A301V/D313E/A324V/Q441E/A537G/N607Kmutation 286 T72A/A137S/V184A/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607Kmutation 287 T72A/A137S/V184G/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607Kmutation 288 T72A/A137S/V184N/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607Kmutation 289 T72A/A137S/V184S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607Kmutation 290 T72A/A137S/V184T/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607Kmutation 324 V184A/V257Ymutation 325 V184A/W187Amutation 326 V184A/N442Dmutation 327 V184P/N442Dmutation 328 V184A/N442D/L439Vmutation 329 A301V/L439V/A537G/N607K/V184Amutation 330 A301V/L439V/A537G/N607K/V184Pmutation 331 A301V/L439V/A537G/N607K/V257Ymutation 332 A301V/L439V/A537G/N607K/W187Amutation 333 A301V/L439V/A537G/N607K/F211Amutation 334 A301V/L439V/A537G/N607K/Q441Emutation 335 A301V/L439V/A537G/N607K/N442Dmutation 336 A301V/L439V/A537G/N607K/V184A/F207Vmutation 337 A301V/L439V/A537G/N607K/V184A/A182Gmutation 338 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/A537G/N607K/V184A/N442Dmutation 339 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/A537G/N607K/V184A/N442D/T185Fmutation 340 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/K83Amutation 341 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/W187Amutation 342 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/F211Amutation 343 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/V178Gmutation 344 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/T185Amutation 345 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/A182Gmutation 346 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/K314Rmutation 347 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/A515Vmutation 348 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/L66Fmutation 349 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/S315Rmutation 350 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/K484Imutation 351 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/V213Amutation 352 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/A245Smutation 353 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/P214Hmutation 354 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/L263Mmutation 355 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/P183Amutation 356 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/T185Kmutation 357 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/T185Dmutation 358 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/T185Cmutation 359 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/T185Smutation 360 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/T185Fmutation 361 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/T185Pmutation 362 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/T185Nmutation 363 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/P183A/A182Gmutation 364 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/P183A/A182Smutation 365 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/T185F/N442Dmutation 366 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/L66F/E80K/I157L/A182G/P214H/L263Mmutation 367 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/L66F/E80K/I157L/A182G/P214H/L263M/Y328Fmutation 368 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/L66F/Y81A/I157L/A182G/P214H/L263M/Y328Fmutation 369 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/L66F/E80K/I157L/A182G/T210L/L263M/Y328Fmutation 370 A301V/L439V/A537G/N607K/Q441Kmutation 371 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/I157Lmutation 372 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/G161Amutation 373 T72A/A137S/Q229P/V257I/A301V/A324V/L439V/Q441E/A537G/N607K/V184A/Y328Fmutation 374 F207V/G226Smutation 375 F207V/W327Gmutation 376 F207V/Y339Hmutation 377 F207V/D619E.

3. A method for designing and producing a mutant protein having a peptide-synthesizing activity comprising: analyzing a protein having an amino acid sequence of SEQ ID NO:208 by X-ray crystal structure analysis to obtain a tertiary structure thereof;predicting a substrate binding site of the protein based on said tertiary structure; andsubstituting, inserting or deleting an amino acid residue located at said substrate binding site.

4. A mutant protein having an amino acid sequence comprising one or more amino acid substitutions, insertions or deletions at positions 67 to 70, 72 to 88, 100, 102, 103, 106, 107, 113 to 117, 130, 155 to 163, 165, 166, 180 to 188, 190 to 195, 200 to 235, 259, 273, 276, 278, 292 to 294, 296, 298, 299, 300 to 304, 325 to 328, 330 to 340, and 437 to 447 in an amino acid sequence in a tertiary structure of a protein having an amino acid sequence of SEQ ID NO:208, and having a peptide-synthesizing activity.

5. A mutant protein of a protein having a peptide-synthesizing activity wherein: three dimensional structures of the mutant protein and a protein having an amino acid sequence of SEQ ID NO:209 are similar as a result of determination by a threading method;in alignment obtained upon the determination, at least one or more amino acid residues are substituted, inserted or deleted at positions corresponding to positions 67 to 70, 72 to 88, 100, 102, 103, 106, 107, 113 to 117, 130, 155 to 163, 165, 166, 180 to 188, 190 to 195, 200 to 235, 259, 273, 276, 278, 292 to 294, 296, 298, 299, 300 to 304, 325 to 328, 330 to 340 and 437 to 447 in the amino acid sequence of SEQ ID NO:209; andsaid mutant protein has the peptide-synthesizing activity.

6. A mutant protein of a protein having a peptide-synthesizing activity wherein: when an alignment of primary sequences of the mutant protein and a protein having an amino acid sequence of SEQ ID NO:209 or an alignment of three dimensional structures of the mutant protein and the protein having the amino acid sequence of SEQ ID NO:209 is performed, homology of the primary sequences is 25% or more, and at least one or more amino acid residues are substituted, inserted or deleted at positions corresponding to positions 67 to 70, 72 to 88, 100, 102, 103, 106, 107, 113 to 117, 130, 155 to 163, 165, 166, 180 to 188, 190 to 195, 200 to 235, 259, 273, 276, 278, 292 to 294, 296, 298, 299, 300 to 304, 325 to 328, 330 to 340 and 437 to 447 in the amino acid sequence of SEQ ID NO:209; andsaid mutant protein has the peptide-synthesizing activity.

7. A mutant protein having one or more changes in a tertiary structure selected from the following (a) to (i) in the tertiary structure of a protein having an amino acid sequence of SEQ ID NO:208, said mutant protein having a peptide-synthesizing activity: (a) at least one or more amino acid residue substitutions, insertions or deletions at any of positions 79 to 82 in the amino acid sequence of SEQ ID NO:208;(b) at least one or more amino acid residue substitutions, insertions or deletions at any of positions 84, 88, 89 and 92 in the amino acid sequence of SEQ ID NO:208;(c) at least one or more amino acid residue substitutions, insertions or deletions at any of positions 72, 75 and 77 in the amino acid sequence of SEQ ID NO:208;(d) at least one or more amino acid residue substitutions, insertions or deletions at any of positions 159, 161, 162, 184, 187 and 276 in the amino acid sequence of SEQ ID NO:208;(e) at least one or more amino acid residue substitutions, insertions or deletions at any of positions 70, 106, 113, 115, 193, 207, 209 to 212, 216 and 259 in the amino acid sequence of SEQ ID NO:208;(f) at least one or more amino acid residue substitutions, insertions or deletions at any of positions 200, 202 to 205, 207 and 228 in the amino acid sequence of SEQ ID NO:208;(g) at least one or more amino acid residue substitutions, insertions or deletions at any of positions 233, 234 and 439 in the amino acid sequence of SEQ ID NO:208;(h) at least one or more amino acid residue substitutions, insertions or deletions at any of positions 328, 339, 340, 445 and 446 in the amino acid sequence of SEQ ID NO:208; and(i) at least one or more amino acid residue substitutions, insertions or deletions at any of positions 87, 155, 157 and 160 in the amino acid sequence of SEQ ID NO: 208.

8. A mutant protein of a protein having a peptide-synthesizing activity wherein: three dimensional structures of the mutant protein and a protein having an amino acid sequence of SEQ ID NO:209 are similar as a result of determination by a threading method, and in alignment obtained upon the determination, one or more changes selected from the following (a′) to (i′) are present; andthe mutant protein has a peptide-synthesizing activity:(a′) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 79 to 82 in the amino acid sequence of SEQ ID NO:209;(b′) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 84, 88, 89 and 92 in the amino acid sequence of SEQ ID NO:209;(c′) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 72, 75 and 77 in the amino acid sequence of SEQ ID NO:209;(d′) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 159, 161, 162, 184, 187 and 276 in the amino acid sequence of SEQ ID NO:209;(e′) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 70, 106, 113, 115, 193, 207, 209 to 212, 216 and 259 in the amino acid sequence of SEQ ID NO:209;(f′) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 200, 202 to 205, 207 and 228 in the amino acid sequence of SEQ ID NO:209;(g′) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 233, 234 and 439 in the amino acid sequence of SEQ ID NO:209;(h′) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 328, 339, 340, 445 and 446 in the amino acid sequence of SEQ ID NO:209; and(i′) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 87, 155, 157 and 160 in the amino acid sequence of SEQ ID NO:209.

9. A mutant protein of a protein having a peptide-synthesizing activity wherein: when an alignment of primary sequences of the mutant protein and a protein having an amino acid sequence of SEQ ID NO:209 or an alignment of three dimensional structures of the mutant protein and the protein having the amino acid sequence of SEQ ID NO:209 is performed, homology of the primary sequences is 25% or more, and one or more changes selected from the following (a″) to (i″) are present; andsaid mutant protein has the peptide-synthesizing activity:(a″) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 79 to 82 in the amino acid sequence of SEQ ID NO:209;(b″) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 84, 88, 89 and 92 in the amino acid sequence of SEQ ID NO:209;(c″) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 72, 75 and 77 in the amino acid sequence of SEQ ID NO:209;(d″) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 159, 161, 162, 184, 187 and 276 in the amino acid sequence of SEQ ID NO:209;(e″) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 70, 106, 113, 115, 193, 207, 209 to 212, 216 and 259 in the amino acid sequence of SEQ ID NO:209;(f″) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 200, 202 to 205, 207 and 228 in the amino acid sequence of SEQ ID NO:209;(g″) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 233, 234 and 439 in the amino acid sequence of SEQ ID NO:209;(h″) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 328, 339, 340, 445 and 446 in the amino acid sequence of SEQ ID NO:209; and(i″) at least one or more amino acid residue substitutions, insertions or deletions in the tertiary structure corresponding to any of positions 87, 155, 157 and 160 in the amino acid sequence of SEQ ID NO:209.

10. A mutant protein having at least one or more amino acid residue substitutions, insertions or deletions at positions 67, 69, 70, 72 to 85, 103, 106, 107, 113 to 116, 165, 182, 183, 185, 187, 188, 190, 200, 202, 204 to 206, 209 to 211, 213 to 235, 301, 328, 338 to 340, 440 to 442 and 446 in a tertiary structure of a protein having an amino acid sequence of SEQ ID NO:208, said mutant protein having a peptide-synthesizing activity.

11. A mutant protein having at least one or more amino acid residue substitutions, insertions or deletions at positions 67, 69, 70, 72 to 84, 106, 107, 114, 116, 183, 185, 187, 188, 202, 204 to 206, 209, 211, 213 to 233, 235, 328, 338 to 442 and 446 in a tertiary structure of a protein having an amino acid sequence of SEQ ID NO:208, said mutant protein having a peptide-synthesizing activity.

12. A mutant protein having at least one or more amino acid residue substitutions, insertions or deletions at positions 67, 70, 72 to 75, 77 to 79, 81 to 84, 114, 116, 185, 188, 202, 204, 206, 209, 211, 213 to 215, 218 to 224, 226 to 233, 235, 328, 338 to 441 and 446 in a tertiary structure of a protein having an amino acid sequence of SEQ ID NO:208, said mutant protein having a peptide-synthesizing activity.

13. A mutant protein having an amino acid sequence comprising one or more mutations selected from any of the following mutations L1 to L335 in an amino acid sequence of SEQ ID NO:208: mutation L1 N67Kmutation L2 N67Lmutation L3 N67Smutation L4 T69Imutation L5 T69Mmutation L6 T69Qmutation L7 T69Rmutation L8 T69Vmutation L9 P70Gmutation L10 P70Nmutation L11 P70Smutation L12 P70Tmutation L13 P70Vmutation L14 A72Cmutation L15 A72Dmutation L16 A72Emutation L17 A72Imutation L18 A72Lmutation L19 A72Mmutation L20 A72Nmutation L21 A72Qmutation L22 A72Smutation L23 A72Vmutation L24 V73Amutation L25 V73Imutation L26 V73Lmutation L27 V73Mmutation L28 V73Nmutation L29 V73Smutation L30 V73Tmutation L31 S74Amutation L32 S74Fmutation L33 S74Kmutation L34 S74Nmutation L35 S74Tmutation L36 S74Vmutation L37 P75Amutation L38 P75Dmutation L39 P75Lmutation L40 P75Smutation L41 Y76Fmutation L42 Y76Hmutation L43 Y76Imutation L44 Y76Vmutation L45 Y76Wmutation L46 G77Amutation L47 G77Fmutation L48 G77Kmutation L49 G77Mmutation L50 G77Nmutation L51 G77Pmutation L52 G77Smutation L53 G77Tmutation L54 Q78Fmutation L55 Q78Lmutation L56 N79Dmutation L57 N79Lmutation L58 N79Rmutation L59 N79Smutation L60 E80Dmutation L61 E80Fmutation L62 E80Lmutation L63 E80Pmutation L64 E80Smutation L65 Y81Amutation L66 Y81Cmutation L67 Y81Dmutation L68 Y81Emutation L69 Y81Fmutation L70 Y81Hmutation L71 Y81Kmutation L72 Y81Lmutation L73 Y81Nmutation L74 Y81Smutation L75 Y81Tmutation L76 Y81Wmutation L77 K82Dmutation L78 K82Lmutation L79 K82Pmutation L80 K82Smutation L81 K83Dmutation L82 K83Fmutation L83 K83Lmutation L84 K83Pmutation L85 K83Smutation L86 K83Vmutation L87 S84Dmutation L88 S84Fmutation L89 S84Kmutation L90 S84Lmutation L91-S84Nmutation L92 S84Qmutation L93 L85Fmutation L94 L85Imutation L95 L85Pmutation L96 L85Vmutation L97 N87Emutation L98 N87Qmutation L99 F88Emutation L100 V103Imutation L101 V103Lmutation L102 K106Amutation L103 K106Fmutation L104 K106Lmutation L105 K106Qmutation L106 K106Smutation L107 W107Amutation L108 W107Ymutation L109 F113Amutation L110 F113Wmutation L111 F113Ymutation L112 E114Amutation L113 E114Dmutation L114 D115Emutation L115 D115Qmutation L116 D115Smutation L117 I116Fmutation L118 I116Kmutation L119 I116Lmutation L120 I116Mmutation L121 I116Nmutation L122 I116Tmutation L123 I116Vmutation L124 I157Kmutation L125 I157Lmutation L126 Y159Gmutation L127 Y159Nmutation L128 Y159Smutation L129 P160Gmutation L130 G161Amutation L131 F162Lmutation L132 F162Ymutation L133 Y163Imutation L134 T165Vmutation L135 Q181Fmutation L136 A182Gmutation L137 A182Smutation L138 P183Amutation L139 P183Gmutation L140 P183Smutation L141 T185Amutation L142 T185Gmutation L143 T185Vmutation L144 W187Amutation L145 W187Fmutation L146 W187Hmutation L147 W187Ymutation L148 Y188Fmutation L149 Y188Lmutation L150 Y188Wmutation L151 G190Amutation L152 G190Dmutation L153 F193Wmutation L154H194Dmutation L155 F200Amutation L156 F200Lmutation L157 F200Smutation L158 F200Vmutation L159 L201Qmutation L160 L201Smutation L161 Q202Amutation L162 Q202Dmutation L163 Q202Fmutation L164 Q202Smutation L165 Q202Tmutation L166 Q202Vmutation L167 D203Emutation L168 A204Gmutation L169 A204Lmutation L170 A204Smutation L171 A204Tmutation L172 A204Vmutation L173 F205Lmutation L174 F205Qmutation L175 F205Vmutation L176 F205Wmutation L177 T206Fmutation L178 T206Kmutation L179 T206Lmutation L180 F207Imutation L181 F207Wmutation L182 F207Ymutation L183 M208Amutation L184 M208Lmutation L185 S209Fmutation L186 S209Kmutation L187 S209Lmutation L188 S209Nmutation L189 S209Vmutation L190 T210Amutation L191 T210Lmutation L192 T210Qmutation L193 T210Vmutation L194 F211Amutation L195 F211Imutation L196 F211Lmutation L197 F211Mmutation L198 F211Vmutation L199 F211Wmutation L200 F211Ymutation L201 G212Amutation L202 V213Dmutation L203 V213Fmutation L204 V213Kmutation L205 V213Smutation L206 P214Dmutation L207 P214Fmutation L208 P214Kmutation L209 P214Smutation L210 R215Amutation L211 R215Imutation L212 R215Kmutation L213 R215Qmutation L214 R215Smutation L215 R215Tmutation L216 R215Ymutation L217 P216Dmutation L218 P216Kmutation L219 K217Dmutation L220 P218Fmutation L221 P218Lmutation L222 P218Qmutation L223 P218Smutation L224 I219Dmutation L225 I219Fmutation L226 I219Kmutation L227 T220Amutation L228 T220Dmutation L229 T220Fmutation L230 T220Kmutation L231 T220Lmutation L232 T220Smutation L233 P221Amutation L234 P221Dmutation L235 P221Fmutation L236 P221Kmutation L237 P221Lmutation L238 P221Smutation L239 D222Amutation L240 D222Fmutation L241 D222Lmutation L242 D222Rmutation L243 Q223Fmutation L244 Q223Kmutation L245 Q223Lmutation L246 Q223Smutation L247 F224Amutation L248 F224Dmutation L249 F224Gmutation L250 F224Kmutation L251 F224Lmutation L252 K225Dmutation L253 K225Gmutation L254 K225Smutation L255 G226Amutation L256 G226Fmutation L257 G226Lmutation L258 G226Nmutation L259 G226Smutation L260 K227Dmutation L261 K227Fmutation L262 K227Smutation L263 I228Amutation L264 I228Fmutation L265 I228Kmutation L266 I228Smutation L267 P229Amutation L268 P229Dmutation L269 P229Kmutation L270 P229Lmutation L271 P229Smutation L272 I230Amutation L273 I230Fmutation L274 I230Kmutation L275 I230Smutation L276 K231Fmutation L277 K231Lmutation L278 K231Smutation L279 E232Dmutation L280 E232Fmutation L281 E232Gmutation L282 E232Lmutation L283 E232Smutation L284 A233Dmutation L285 A233Fmutation L286 A233Hmutation L287 A233Kmutation L288 A233Lmutation L289 A233Nmutation L290 A233Smutation L291 D234Lmutation L292 D234Smutation L293 K235Dmutation L294 K235Fmutation L295 K235Lmutation L296 K235Smutation L297 F259Ymutation L298 R276Amutation L299 R276Qmutation L300 A298Smutation L301 D300Nmutation L302 V301Mmutation L303 Y328Fmutation L304 Y328Hmutation L305 Y328Mmutation L306 Y328Wmutation L307 W332Hmutation L308 E336Amutation L309 N338Amutation L310 N338Fmutation L311 Y339Kmutation L312 Y339Lmutation L313 Y339Tmutation L314 L340Amutation L315 L340Imutation L316 L340Vmutation L317 V439Pmutation L318 I440Fmutation L319 I440Vmutation L320 E441Fmutation L321 E441Mmutation L322 E441Nmutation L323 N442Amutation L324 N442Lmutation L325 R443Smutation L326 T444Wmutation L327 R445Gmutation L328 R445Kmutation L329 E446Amutation L330 E446Fmutation L331 E446Qmutation L332 E446Smutation L333 E446Tmutation L334 Y447Lmutation L335 Y447S.

14. A mutant protein having an amino acid sequence comprising one or more mutations selected from any of the following mutations M1 to M642 in an amino acid sequence of SEQ ID NO:208: mutation M1 T69N/I157Lmutation M2 T69Q/I157Lmutation M3 T69S/I157Lmutation M4 P70A/I157Lmutation M5 P70G/I157Lmutation M6 P70I/I157Lmutation M7 P70L/I157Lmutation M8 P70N/I157Lmutation M9 P70S/I157Lmutation M10 P70T/I157Lmutation M11 P70T/T210Lmutation M12 P70T/Y328Fmutation M13 P70V/I157Lmutation M14 A72E/G77Smutation M15 A72E/E80Dmutation M16 A72E/Y81Amutation M17 A72E/S84Dmutation M18 A72E/F113Wmutation M19 A72E/I157Lmutation M20 A72E/G161Amutation M21 A72E/F162Lmutation M22 A72E/A184Gmutation M23 A72E/W187Fmutation M24 A72E/F200Amutation M25 A72E/A204Smutation M26 A72E/T210Lmutation M27 A72E/F211Lmutation M28 A72E/F211Wmutation M29 A72E/G226Amutation M30 A72E/I228Kmutation M31 A72E/A233Dmutation M32 A72E/Y328Fmutation M33 A72S/I157Lmutation M34 A72V/Y328Fmutation M35 V73A/I157Lmutation M36 V73I/I157Lmutation M37 S74A/I157Lmutation M38 S74N/I157Lmutation M39 S74T/I157Lmutation M40 S74V/I157Lmutation M41 G77A/I157Lmutation M42 G77F/I157Lmutation M43 G77M/I157Lmutation M44 G77P/I157Lmutation M45 G77S/E80Dmutation M46 G77S/Y81Amutation M47 G77S/S84Dmutation M48 G77S/F113Wmutation M49 G77S/I157Lmutation M50 G77S/Y159Nmutation M51 G77S/Y159Smutation M52 G77S/G161Amutation M53 G77S/F162Lmutation M54 G77S/A184Gmutation M55 G77S/W187Fmutation M56 G77S/F200Amutation M57 G77S/A204Smutation M58 G77S/T210Lmutation M59 G77S/F211Lmutation M60 G77S/F211Wmutation M61 G77S/I228Kmutation M62 G77S/A233Dmutation M63 G77S/R276Amutation M64 G77S/Y328Fmutation M65 E80D/Y81Amutation M66 E80D/F113Wmutation M67 E80D/I157Lmutation M68 E80D/Y159Nmutation M69 E80D/G161Amutation M70 E80D/A184Gmutation M71 E80D/F211Wmutation M72 E80D/Y328Fmutation M73 E80S/I157Lmutation M74 Y81A/F113Wmutation M75 Y81A/I157Lmutation M76 Y81A/Y159Nmutation M77 Y81A/Y159Smutation M78 Y81A/G161Amutation M79 Y81A/A184Gmutation M80 Y81A/W187Fmutation M81 Y81A/F200Amutation M82 Y81A/T210Lmutation M83 Y81A/F211Wmutation M84 Y81A/F211Ymutation M85 Y81A/G226Amutation M86 Y81A/I228Kmutation M87 Y81A/A233Dmutation M88 Y81A/Y328Fmutation M89 Y81H/I157Lmutation M90 Y81N/I157Lmutation M91 K83P/I157Lmutation M92 S84A/I157Lmutation M93 S84D/F-13Wmutation M94 S84D/I157Lmutation M95 S84D/Y159Nmutation M96 S84D/G161Amutation M97 S84D/A184Gmutation M98 S84D/Y328Fmutation M99 S84E/I157Lmutation M100 S84F/I157Lmutation M101 S84K/I157Lmutation M102 L85F/I157Lmutation M103 L85I/I157Lmutation M104 L85P/I157Lmutation M105 L85V/I157Lmutation M106 N87A/I157Lmutation M107 N87D/I157Lmutation M108 N87E/I157Lmutation M109 N87G/I157Lmutation M110 N87Q/I157Lmutation M111 N87S/I157Lmutation M112 F88A/I157Lmutation M113 F88D/I157Lmutation M114 F88E/I157Lmutation M115 F88E/Y328Fmutation M116 F88L/I157Lmutation M117 F88T/I157Lmutation M118 F88V/I157Lmutation M119 F88Y/I157Lmutation M120 K106H/I157Lmutation M121 K106L/I157Lmutation M122 K106M/I157Lmutation M123 K106Q/I157Lmutation M124 K106R/I157Lmutation M125 K106S/I157Lmutation M126 K106V/I157Lmutation M127 W107A/I157Lmutation M128 W107A/Y328Fmutation M129 W107Y/I157Lmutation M130 W107Y/T206Ymutation M131 W107Y/K217Dmutation M132 W107Y/P218Lmutation M133 W107Y/T220Lmutation M134 W107Y/P221Dmutation M135 W107Y/Y328Fmutation M136 F113A/I157Lmutation M137 F113H/I157Lmutation M138 F113N/I157Lmutation M139 F113V/I157Lmutation M140 F113W/I157Lmutation M141 F113W/Y159Nmutation M142 F113W/Y159Smutation M143 F113W/G161Amutation M144 F113W/F162Lmutation M145 F113W/A184Gmutation M146 F113W/W187Fmutation M147 F113W/F200Amutation M148 F113W/T206Ymutation M149 F113W/T210Lmutation M150 F113W/F211Lmutation M151 F113W/F211Wmutation M152 F113W/F211Ymutation M153 F113W/V213Dmutation M154 F113W/K217Dmutation M155 F113W/T220Lmutation M156 F113W/P221Dmutation M157 F113W/G226Amutation M158 F113W/I228Kmutation M159 F113W/A233Dmutation M160 F113W/R276Amutation M161 F113Y/I157Lmutation M162 F113Y/F211Wmutation M163 E114D/I157Lmutation M164 D115A/I157Lmutation M165 D115E/I157Lmutation M166 D115M/I157Lmutation M167 D115N/I157Lmutation M168 D115Q/I157Lmutation M169 D115S/I157Lmutation M170 D115V/I157Lmutation M171 I157L/Y159Imutation M172 I157L/Y159Lmutation M173 I157L/Y159Nmutation M174 I157L/Y159Smutation M175 I157L/Y159Vmutation M176 I157L/P160Amutation M177 I157L/P160Smutation M178 I157L/G161Amutation M179 I157L/F162Lmutation M180 I157L/F162Mmutation M181 I157L/F162Nmutation M182 I157L/F162Ymutation M183 I157L/T165Lmutation M184 I157L/T165Vmutation M185 I157L/Q181Amutation M186 I157L/Q181Fmutation M187 I157L/Q181Nmutation M188 I157L/A184Gmutation M189 I157L/A184Lmutation M190 I157L/A184Mmutation M191 I157L/A184Smutation M192 I157L/A184Tmutation M193 I157L/W187Fmutation M194 I157L/W187Ymutation M195 I157L/F193Hmutation M196 I157L/F193Imutation M197 I157L/F193Wmutation M198 I157L/F200Amutation M199 I157L/F200Hmutation M200 I157L/F200Lmutation M201 I157L/F200Ymutation M202 I157L/A204Gmutation M203 I157L/A204Imutation M204 I157L/A204Lmutation M205 I157L/A204Smutation M206 I157L/A204Tmutation M207 I157L/A204Vmutation M208 I157L/F205Amutation M209 I157L/F207Imutation M210 I157L/F207Mmutation M211 I157L/F207Vmutation M212 I157L/F207Wmutation M213 I157L/F207Ymutation M214 I157L/M208Amutation M215 I157L/M208Kmutation M216 I157L/M208Lmutation M217 I157L/M208Tmutation M218 I157L/M208Vmutation M219 I157L/S209Fmutation M220 I157L/S209Nmutation M221 I157L/T210Amutation M222 I157L/T210Lmutation M223 I157L/F211Imutation M224 I157L/F211Lmutation M225 I157L/F211Vmutation M226 I157L/F211Wmutation M227 I157L/G212Amutation M228 I157L/G212Dmutation M229 I157L/G212Smutation M230 I157L/R215Kmutation M231 I157L/R215Lmutation M232 I157L/R215Tmutation M233 I157L/R215Ymutation M234 I157L/T220Lmutation M235 I157L/G226Amutation M236 I157L/G226Fmutation M237 I157L/I228Kmutation M238 I157L/A233Dmutation M239 I157L/R276Amutation M240 I157L/Y328Amutation M241 I157L/Y328Fmutation M242 I157L/Y328Hmutation M243 I157L/Y328Imutation M244 I157L/Y328Lmutation M245 I157L/Y328Pmutation M246 I157L/Y328Vmutation M247 I157L/Y328Wmutation M248 I157L/L340Fmutation M249 I157L/L340Imutation M250 I157L/L340Vmutation M251 I157L/V439Amutation M252 I157L/V439Pmutation M253 I157L/R445Amutation M254 I157L/R445Fmutation M255 I157L/R445Gmutation M256 I157L/R445Kmutation M257 I157L/R445Vmutation M258 Y159N/G161Amutation M259 Y159N/A184Gmutation M260 Y159N/A204Smutation M261 Y159N/T210Lmutation M262 Y159N/F211Wmutation M263 Y159N/F211Ymutation M264 Y159N/G226Amutation M265 Y159N/I228Kmutation M266 Y159N/A233Dmutation M267 Y159N/Y328Fmutation M268 Y159S/G161Amutation M269 Y159S/F211Wmutation M270 G161A/F162Lmutation M271 G161A/A184Gmutation M272 G161A/W187Fmutation M273 G161A/F200Amutation M274 G161A/A204Smutation M275 G161A/T210Lmutation M276 G161A/F211Lmutation M277 G161A/F211Wmutation M278 G161A/G226Amutation M279 G161A/I228Kmutation M280 G161A/A233Dmutation M281 G161A/Y328Fmutation M282 F162L/A184Gmutation M283 F162L/F211Wmutation M284 F162L/A233Dmutation M285 P183A/Y328Fmutation M286 A184G/W187Fmutation M287 A184G/F200Amutation M288 A184G/A204Smutation M289 A184G/T210Lmutation M290 A184G/F211Lmutation M291 A184G/F211Wmutation M292 A184G/I228Kmutation M293 A184G/A233Dmutation M294 A184G/R276Amutation M295 V184G/Y328Fmutation M296 T185A/Y328Fmutation M297 T185N/Y328Fmutation M298 W187F/F211Wmutation M299 W187F/Y328Fmutation M300 F193W/F211Wmutation M301 F200A/F211Wmutation M302 F200A/Y328Fmutation M303 L201Q/Y328Fmutation M304 L201S/Y328Fmutation M305 A204S/F211Wmutation M306 A204S/Y328Fmutation M307 T210L/F211Wmutation M308 T210L/Y328Fmutation M309 F211L/A233Dmutation M310 F211L/Y328Fmutation M311 F211W/I228Kmutation M312 F211W/A233Dmutation M313 F211W/Y328Fmutation M314 R215A/Y328Fmutation M315 R215L/Y328Fmutation M316 T220L/A233Dmutation M317 T220L/D300Nmutation M318 P221L/A233Dmutation M319 P221L/Y328Fmutation M320 F224A/A233Dmutation M321 G226A/Y328Fmutation M322 G226F/A233Dmutation M323 G226F/Y328Fmutation M324 I228K/Y328Fmutation M325 A233D/K235Dmutation M326 A233D/Y328Fmutation M327 R276A/Y328Fmutation M328 Y328F/Y339Fmutation M329 A27T/Y81A/S84Dmutation M330 P70T/A72E/I157Lmutation M331 P70T/G77S/I157Lmutation M332 P70T/E80D/F88Emutation M333 P70T/Y81A/I157Lmutation M334 P70T/S84D/I157Lmutation M335 P70T/F88E/Y328Fmutation M336 P70T/F113W/I157Lmutation M337 P70T/I157L/A204Smutation M338 P70T/I157L/T210Lmutation M339 P70T/I157L/A233Dmutation M340 P70T/I157L/Y328Fmutation M341 P70T/I157L/V439Pmutation M342 P70T/I157L/1440Fmutation M343 P70T/G161A/T210Lmutation M344 P70T/G161A/Y328Fmutation M345 P70T/A184G/W187Fmutation M346 P70T/A204S/Y328Fmutation M347 P70T/F211W/Y328Fmutation M348 P70V/A72E/I157Lmutation M349 A72E/S74T/I157Lmutation M350 A72E/G77S/Y328Fmutation M351 A72E/E80D/Y328Fmutation M352 A72E/Y81H/I157Lmutation M353 A72E/K83P/I157Lmutation M354 A72E/S84D/Y328Fmutation M355 A72E/L85P/I157Lmutation M356 A72E/F113W/I157Lmutation M357 A72E/F113W/Y328Fmutation M358 A72E/F113Y/I157Lmutation M359 A72E/D115Q/I157Lmutation M360 A72E/I157L/G161Amutation M361 A72E/I157L/F162Lmutation M362 A72E/I157L/A184Gmutation M363 A72E/I157L/F200Amutation M364 A72E/I157L/A204Smutation M365 A72E/I157L/A204Tmutation M366 A72E/I157L/T210Lmutation M367 A72E/I157L/F211Wmutation M368 A72E/I157L/G226Amutation M369 A72E/I157L/A233Dmutation M370 A72E/I157L/Y328Fmutation M371 A72E/I157L/L340Vmutation M372 A72E/I157L/V439Pmutation M373 A72E/G161A/Y328Fmutation M374 A72E/F162L/Y328Fmutation M375 A72E/A184G/Y328Fmutation M376 A72E/W187F/Y328Fmutation M377 A72E/F200A/Y328Fmutation M378 A72E/A204S/Y328Fmutation M379 A72E/T210L/Y328Fmutation M380 A72E/I228K/Y328Fmutation M381 A72E/A233D/Y328Fmutation M382 A72E/Y328F/Y159Nmutation M383 A72E/Y328F/F211Wmutation M384 A72E/Y328F/F211Ymutation M385 A72E/Y328F/G226Amutation M386 A72V/Y81A/Y328Fmutation M387 A72V/G161A/Y328Fmutation M388 G77M/I157L/T210Lmutation M389 G77P/I157L/F162Lmutation M390 G77P/I157L/A184Gmutation M391 G77P/F211W/Y328Fmutation M392 G77S/Y81A/Y328Fmutation M393 G77S/S84D/I157Lmutation M394 G77S/F88E/I157Lmutation M395 G77S/F113W/I157Lmutation M396 G77S/F113Y/I157Lmutation M397 G77S/D115Q/I157Lmutation M398 G77S/I157L/G161Amutation M399 G77S/I157L/F200Amutation M400 G77S/I157L/A204Smutation M401 G77S/I157L/T210Lmutation M402 G77S/I157L/F211Wmutation M403 G77S/I157L/G226Amutation M404 G77S/I157L/A233Dmutation M405 G77S/I157L/L340Vmutation M406 G77S/I157L/V439Pmutation M407 G77S/G161A/Y328Fmutation M408 E80D/Y81A/Y328Fmutation M409 Y81A/S84D/Y328Fmutation M410 Y81A/F113W/Y328Fmutation M411 Y81A/I157L/T210Lmutation M412 Y81A/I157L/Y328Fmutation M413 Y81A/G161A/Y328Fmutation M414 Y81A/F162L/Y328Fmutation M415 Y81A/A184G/Y328Fmutation M416 Y81A/W187F/Y328Fmutation M417 Y81A/A204S/Y328Fmutation M418 Y81A/T210L/Y328Fmutation M419 Y81A/I228K/Y328Fmutation M420 Y81A/A233D/Y328Fmutation M421 Y81A/Y328F/Y159Nmutation M422 Y81A/Y328F/Y159Smutation M423 Y81A/Y328F/F211Wmutation M424 Y81A/Y328F/F211Ymutation M425 Y81A/Y328F/G226Amutation M426 Y81A/Y328F/R276Amutation M427 K83P/I157L/A184Gmutation M428 K83P/I157L/T210Lmutation M429 K83P/F211W/Y328Fmutation M430 S84D/F113W/I157Lmutation M431 S84D/I157L/T210Lmutation M432 F88E/I157L/F162Lmutation M433 F88E/I157L/A184Gmutation M434 F88E/I157L/F200Amutation M435 F88E/I157L/T210Lmutation M436 F88E/I157L/Y328Fmutation M437 F88E/I157L/Y328Qmutation M438 F88E/I157L/L340Vmutation M439 F88E/T210L/Y328Fmutation M440 F88E/F211W/Y328Fmutation M441 F113W/I157L/G161Amutation M442 F113W/I157L/A184Gmutation M443 F113W/I157L/W187Fmutation M444 F113W/I157L/F200Amutation M445 F113W/I157L/A204Smutation M446 F113W/I157L/A204Tmutation M447 F113W/I157L/T210Lmutation M448 F113W/I157L/F211Wmutation M449 F113W/I157L/G226Amutation M450 F113W/I157L/A233Dmutation M451 F113W/I157L/Y328Fmutation M452 F113W/I157L/L340Vmutation M453 F113W/I157L/V439Pmutation M454 F113W/G161A/T210Lmutation M455 F113W/G161A/Y328Fmutation M456 F113W/A184G/W187Fmutation M457 F113Y/I157L/T210Lmutation M458 F113Y/I157L/Y328Fmutation M459 F113Y/G161A/T210Lmutation M460 D115Q/I157L/T210Lmutation M461 D115Q/I157L/Y328Fmutation M462 I157L/Y159N/T210Lmutation M463 I157L/Y159N/Y328Fmutation M464 I157L/G161A/W187Fmutation M465 I157L/G161A/F200Amutation M466 I157L/G161A/A204Smutation M467 I157L/G161A/T210Lmutation M468 I157L/G161A/A233Dmutation M469 I157L/G161A/Y328Fmutation M470 I157L/F162L/A184Gmutation M471 I157L/F162L/T210Lmutation M472 I157L/F162L/L340Vmutation M473 I157L/A184G/W187Fmutation M474 I157L/A184G/F200Amutation M475 I157L/A184G/A204Tmutation M476 I157L/A184G/T210Lmutation M477 I157L/A184G/F211Wmutation M478 I157L/A184G/L340Vmutation M479 I157L/W187F/T210Lmutation M480 I157L/W187F/Y328Fmutation M481 I157L/F200A/T210Lmutation M482 I157L/F200A/Y328Fmutation M483 I157L/A204S/T210Lmutation M484 I157L/A204S/Y328Fmutation M485 I157L/A204T/T210Lmutation M486 I157L/A204T/Y328Fmutation M487 I157L/T210L/F211Wmutation M488 I157L/T210L/G212Amutation M489 I157L/T210L/G226Amutation M490 I157L/T210L/A233Dmutation M491 I157L/T210L/Y328Fmutation M492 I157L/T210L/L340Vmutation M493 I157L/T210L/V439Pmutation M494 I157L/F211W/Y328Fmutation M495 I157L/G226A/Y328Fmutation M496 I157L/A233D/Y328Fmutation M497 I157L/Y328F/L340Vmutation M498 I157L/Y328F/V439Pmutation M499 Y159N/F211W/Y328Fmutation M500 G161A/A184G/W187Fmutation M501 G161A/T210L/Y328Fmutation M502 G161A/F211W/Y328Fmutation M503 A182G/P183A/Y328Fmutation M504 A182S/P183A/Y328Fmutation M505 A184G/W187F/F200Amutation M506 A184G/W187F/A204Smutation M507 A184G/W187F/F211Wmutation M508 A184G/W187F/I228Kmutation M509 A184G/W187F/A233Dmutation M510 F200A/F211W/Y328Fmutation M511 A204S/F211W/Y328Fmutation M512 A204T/F211W/Y328Fmutation M513 F211W/Y328F/L340Vmutation M514 P70T/A72E/I157L/Y328Fmutation M515 P70T/A72E/T210L/Y328Fmutation M516 P70T/G77M/I157L/Y328Fmutation M517 P70T/Y81A/I157L/T210Lmutation M518 P70T/Y81A/I157L/Y328Fmutation M519 P70T/S84D/I157L/Y328Fmutation M520 P70T/F88E/I157L/Y328Fmutation M521 P70T/F88E/T210L/Y328Fmutation M522 P70T/F113W/I157L/T210Lmutation M523 P70T/F113W/G161A/Y328Fmutation M524 P70T/F113Y/I157L/Y328Fmutation M525 P70T/D115Q/I157L/T210Lmutation M526 P70T/D115Q/I157L/Y328Fmutation M527 P70T/I157L/G161A/T210Lmutation M528 P70T/I157L/A184G/W187Fmutation M529 P70T/I157L/A184G/T210Lmutation M530 P70T/I157L/W187F/T210Lmutation M531 P70T/I157L/W187F/Y328Fmutation M532 P70T/I157L/A204T/T210Lmutation M533 P70T/I157L/A204T/Y328Fmutation M534 P70T/I157L/A204T/T210Lmutation M535 P70T/I157L/T210L/F211Wmutation M536 P70T/I157L/T210L/G226Amutation M537 P70T/I157L/T210L/A233Dmutation M538 P70T/I157L/T210L/Y328Fmutation M539 P70T/I157L/T210L/L340Vmutation M540 P70T/I157L/T210L/V439Pmutation M541 P70T/I157L/Y328F/V439Pmutation M542 P70T/G161A/T210L/Y328Fmutation M543 P70T/G161A/A233D/Y328Fmutation M544 A72E/S74T/I157L/Y328Fmutation M545 A72E/G77S/F113W/I157Lmutation M546 A72E/Y81H/I157L/Y328Fmutation M547 A72E/K83P/I157L/Y328Fmutation M548 A72E/F88E/F113W/I157Lmutation M549 A72E/F88E/I157L/Y328Fmutation M550 A72E/F88E/G161A/Y328Fmutation M551 A72E/F113W/I157L/Y328Fmutation M552 A72E/F113W/G161A/Y328Fmutation M553 A72E/F113Y/I157L/Y328Fmutation M554 A72E/F113Y/G161A/Y328Fmutation M555 A72E/F113Y/G226A/Y328Fmutation M556 A72E/I157L/G161A/Y328Fmutation M557 A72E/I157L/F162L/Y328Fmutation M558 A72E/I157L/A184G/Y328Fmutation M559 A72E/I157L/F200A/Y328Fmutation M560 A72E/I157L/A204T/Y328Fmutation M561 A72E/I157L/F211W/Y328Fmutation M562 A72E/I157L/F211Y/Y328Fmutation M563 A72E/I157L/A233D/Y328Fmutation M564 A72E/I157L/Y328F/L340Vmutation M565 A72E/G161A/A204T/Y328Fmutation M566 A72E/G161A/T210L/Y328Fmutation M567 A72E/G161A/F211W/Y328Fmutation M568 A72E/G161A/F211Y/Y328Fmutation M569 A72E/G161A/A233D/Y328Fmutation M570 A72E/G161A/Y328F/L340Vmutation M571 A72E/A184G/W187F/Y328Fmutation M572 A72E/T210L/Y328F/L340Vmutation M573 A72V/I157L/W187F/Y328Fmutation M574 G77P/I157L/T210L/Y328Fmutation M575 Y81A/S84D/I157L/Y328Fmutation M576 Y81A/F88E/I157L/Y328Fmutation M577 Y81A/F113W/I157L/Y328Fmutation M578 Y81A/I157L/G161A/Y328Fmutation M579 Y81A/I157L/W187F/Y328Fmutation M580 Y81A/I157L/A204S/Y328Fmutation M581 Y81A/I157L/T210L/Y328Fmutation M582 Y81A/I157L/A233D/Y328Fmutation M583 Y81A/I157L/Y328F/V439Pmutation M584 Y81A/A184G/W187F/Y328Fmutation M585 F88E/I157L/T210L/Y328Fmutation M586 F88E/I157L/A233D/Y328Fmutation M587 F113W/I157L/A204T/T210Lmutation M588 F113W/I157L/T210L/Y328Fmutation M589 I157L/G161A/A184G/W187Fmutation M590 I157L/G161A/T210L/Y328Fmutation M591 I157L/A184G/W187F/T210Lmutation M592 I157L/A204S/T210L/Y328Fmutation M593 I157L/A204T/T210L/Y328Fmutation M594 I157L/T210L/A233D/Y328Fmutation M595 G161A/A184G/W187F/Y328Fmutation M596 P70T/A72E/S84D/I157L/Y328Fmutation M597 P70T/A72E/A204S/I157L/Y328Fmutation M598 P70T/A72E/T210L/I157L/Y328Fmutation M599 P70T/A72E/G226A/I157L/Y328Fmutation M600 P70T/A72E/A233D/I157L/Y328Fmutation M601 P70T/Y81A/I157L/T210L/Y328Fmutation M602 P70T/Y81A/I157L/A233D/Y328Fmutation M603 P70T/Y81A/I157L/T210L/Y328Fmutation M604 P70T/Y81A/A233D/I157L/Y328Fmutation M605 P70T/S84D/I157L/T210L/Y328Fmutation M606 P70T/F113W/I157L/T210L/Y328Fmutation M607 P70T/I157L/A184G/W187F/A233Dmutation M608 P70T/I157L/W187F/T210L/Y328Fmutation M609 P70T/I157L/A204S/T210L/Y328Fmutation M610 P70T/G161A/A184G/W187F/Y328Fmutation M611 P70V/A72E/F113Y/I157L/Y328Fmutation M612 P70V/A72E/I157L/F211W/Y328Fmutation M613 A72E/S74T/F113Y/I157L/Y328Fmutation M614 A72E/S74T/I157L/F211W/Y328Fmutation M615 A72E/Y81H/I157L/F211W/Y328Fmutation M616 A72E/K83P/F113Y/I157L/Y328Fmutation M617 A72E/W17F/F113Y/I157L/Y328Fmutation M618 A72E/F113Y/D115Q/I157L/Y328Fmutation M619 A72E/F113Y/I157L/Y328F/L340Vmutation M620 A72E/F113Y/I157L/Y328F/V439Pmutation M621 A72E/F113Y/G161A/I157L/Y328Fmutation M622 A72E/F113Y/A204S/I157L/Y328Fmutation M623 A72E/F113Y/A204T/I157L/Y328Fmutation M624 A72E/F113Y/T210L/I157L/Y328Fmutation M625 A72E/F113Y/A233D/I157L/Y328Fmutation M626 A72E/I157L/G161A/F162L/Y328Fmutation M627 A72E/I157L/W187F/F211W/Y328Fmutation M628 A72E/I157L/A204S/F211W/Y328Fmutation M629 A72E/I157L/A204T/F211W/Y328Fmutation M630 A72E/I157L/F211W/Y328F/L340Vmutation M631 A72E/I157L/F211W/Y328F/V439Pmutation M632 A72E/I157L/G226A/F211W/Y328Fmutation M633 A72E/I157L/A233D/F211W/Y328Fmutation M634 Y81A/S84D/I157L/T210L/Y328Fmutation M635 Y81A/I157L/A184G/W187F/Y328Fmutation M636 Y81A/I157L/A184G/W187F/T210Lmutation M637 Y81A/I157L/A233D/T210L/Y328Fmutation M638 F88E/I157L/A184G/W187F/T210Lmutation M639 F113Y/I157L/Y159N/F211W/Y328Fmutation M640 I157L/A184G/W187F/T210L/Y328Fmutation M641 P70T/I157L/A184G/W187F/T210L/Y328Fmutation M642 Y81A/I157L/A184G/W187F/T210L/Y328F.