本発明は、pckA遺伝子が修飾または欠失されている
Contents
1. 7 JP 2007 532114 A 2007 11 15 HHHHHHHHHHH O O E d d dd Addo dd 0000070 HHHHHHH I2. 68 JP 2007 532114 A 2007 11 15 I I0000000000000000000000 HHHHHHHHHH HHHHHHHHHHH OOTD IU O HHHHHHHHHHH ii HHHHHHHHHHHHHHHHHHHHHH l ig O HHHHHHHHHHH ii HHHHHHHHHHHHH
3. 16 JP 2007 532114 A 2007 11 15
4. HHHHHHH HHHHHHHHHHHHHHHH HHHHHHH OD HHHHHHH HHHHHHHHHHHHHHHH UU HHHHHHHHHHHHHHHH 00 8 H PE D DH 8 HHHHHHHHHHH UU HHHHHHH HHHHHHHHHHHHHHHH HHHHHHH HHHHHHHHHHHHHHH HHHHHHH HHHHHHHHHHH 00000 VULUUDUUU OOOOOOg 1000000000 0000800000050 O BN OO IlHHHHHHHHHHH 10 20 30 50 JP 2007 532114 A 2007 11 15
5. 10 20 30 50 JP 2007 532114 A 2007 11 15 13 10 20 30
6. x C C N TEI EIT N EITTIE II EO x D n 91 JP 2007 532114 A 2007 11
7. 14 JP 2007 532114 A 2007 11 15 10 20 30 50 JP 2007 532114 A 2007 11 15 15 10 20 30
8. 10 20 30 50 19 JP 2007 532114 A 2007 11 15 1000000000 40 20 30 50 JP 2007 532114 A 2007 11 15 20 10 HHHHHHHH
9. 10 20 30 50 87 JP 2007 532114 A 2007 11 15 GGGGATCTCTGCAGTGAGATCTGGTAATGACTCTCTAGCTTGAGGCATCAAATAAAACGAAAG GCTCAGTCGAAAGACTGGGCCTTTCGTTTTATCTGTTGTTTGTCGGTGAACGCTCTCCTGAGTA GGACAAATCCGCCGCTCTAGCTAAGCAGAAGGCCATCCTGACGGATGGCCTTTTTGCGTTTCT ACAAACTCTTGTTAACTCTAGAGCTGCCTGCCGCGTTTCGGTGATGAAGATCTTCCCGATGATT AATTAATTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATGCAGCAATGGCAAGAACGTTGC TCTAGAATAATTCTACACAGCCCAGTCCAGACTATTCGGCACTGAAATTATGGGTGAAGTGGTC AAGACCTCACTAGGCACCTTAAAAATAGCGCACCCTGAAGAAGATTTATTTGAGGTAGCCCTT GCCTACCTAGCTTCCAAGAAAGATATCCTAACAGCACAAGAGCGGAAAGATGTTTTGTTCTACA TCCAGAACAAC
10. E bago z E E nm n an EA m A Ey Gn Ed in nnnnnnnnnnnnnm 5 Gabe ee i en ee uae 10 20 30 50 JP 2007 532114 A 2007 11 15 30 10 20 30 50 DU O D C C C EN B HO C C C
11. 0000 B 10 20 30 50 74 JP 2007 532114 A 2007 11 15 10 20
12. 10 20 30 50 JP 2007 532114 A 2007 11 15 23 10 20 D 30 JP 2007 532114 A 2007 11 15 24 10 20
13. ATGAATTTTCAAACAATCGAGCTTGACACATGGTATAGAAAATCTTATTTTGACCATTA CATGAAGGAAGCGAAATGTTCTTTCAGCATCACGGCAAACGTCAATGTGACAAATTTG CTCGCCGTGCTCAAGAAAAAGAAGCTCAAGCTGTATCCGGCTTTTATTTATATCGTAT CAAGGGTCATTCATTCGCGCCCTGAGTTTAGAACAACGTTTGATGACAAAGGAAGCT GGGTTATTGGGAACAAATGCATCCGTGCTATGCGATTTTTCATCAGGACGACCAAAC GTTTTCCGCCCTCTGGACGGAATACTCAGACGATTTTTCGCAGTTTTATCATCAATAT CTTCTGGACGCCGAGCGCTTTGGAGACAAAAGGGGCCTTTGGGCTAAGCCGGACAT CCCGCCCAATACGTTTTCAGTTTCTTCTATTCCATGGGTGCGCTTTTCAACATTCAATT TAAACCTTGATAACAGCGAACACTTGCTGCCGATTATTACAAACGGGAAATACTTTTC AGAAGGCAGGGAAACATTTTTGCCCGTTTCCTGCAAGTTCACCATGCAGTGTGTGAC GGCTATCATGCCGGCGCTTTTATAA SEQ ID NO 58 100000 0 OD 1000 MNFQTIELDTWYRKSYFDHYMKEAKCSFSITANVNVTNLLAVLKKKKLKLYPAF IYIVSRVI HSRPEFRTTFDDKGQLGYWEQMHPCYAIF HQDDQTFSALWTEYSDDFSQFYHQYLLDA ERFGDKRGLWAKPDIPPNTFSVSSIPWVRFSTFNLNLDNSEHLLPIITNGKYFSEGRETF L PVSCKFTMQCVTAIMPALL SEQ ID NO 59 O III I Ub
14. 50 HHHHHHHHHHHHHHHH ui JP 2007 532114 A 2007 11 15
15. 72 JP 2007 532114 A 2007 11 15 n nanana ae 5 10 20 30 50 73 JP 2007 532114 A 2007 11 15
16. 11 JP 2007 532114 A 2007 11 15 10 20 30 50 12 JP 2007 532114 A 2007 11 15
17. UI JP 2007 532114 A 2007 11 15 10 10 20 LER ETAT A D 30 IU
18. 000 O U Og U 10 20 30 50 2007 532114 A 2007 11
19. 30 C 50 93 JP 2007 532114 A 2007 11 15 III III III III III III III III III III III IU
20. 10 20 30 77 JP 2007 532114 A 2007 11 15 X1 TGA 7 2 sy TIT KIIRE CTACATTCTAGACGATTTGTTTGATCGATATGTGGAAGC GGCTGAGGATCCATTCCTCAGCCCAGAAGAGAACCTA TCCCTCGGATCCGAAATAGGTTCTGCTTATTGTATTOG AGCGTTGAGCTCGCGCCATGCCATTATATTGGCTGCTG GTGACGGAATTCCACGTGCGTCTTATATTGCTGAGCTT CGTTTTGGATCCAAAAACACCCCTTTAGATAATCTTAT gt eb ATCAAAGGATCCGCTATGCTCCAAATGTACACCTTTCCGT Pphage 1 Psd TATTTCTGCAGGCTGATATAAATAATACTGTGTGTTCC 67 ATCTTGAATTCAAAGGGTACAAGCACAGAGACAGAG GACTTGGATCCGGTAAGTGGGCAGTTTGTGGGCAGT 61 62 63 64 65 x lt TAGATAGGATCCTATTGAAAACTGTTTAAGAAGAGGA 70 Pphage 2 Pst CTGATTCTGCAGGAGTGTTTITGAAGGAAGCTTCATT 71 CTCCGCGGTACCGTCACGAATGCGCCTCTTATTCTAT 72 BamHI TCGCTGGGATCCTTGGCGCCGTGGAATCGATTTTGTCC 73 CAATGGGATCCTATATCAACGGTTATGAATTCACAA 174 CAGAACTGCAGGAGCGAGGCGTCTCGCTGCCTGAAA 75 Pphage 4 BamHI 505 Pai O p00000 78 JP 2007 532114 A 2007 11 15 1 PPS UF Tsai PPSUR PPSDR SPB UF Saci ACTGATGAGCTCTGCCTAAACAGCARACAGCAGAAC amp SPBUR BamHI ACGAATGGATGGATCATAAAGCCGGAGCAGATTAAAT
21. DU IU JP 2007 532114 A 2007 11 15 70 10 20 30 D HHHHHHHHHHHHHH 00000 50 IU D loo n
22. 42 JP 2007 532114 A 2007 11 15 000 ATGAAATTGAAATCTAAGTTGTTTGTTATTTGTTTGGCCGCAGCCGCGATTTTTACAGCG GCTGGCGTTTCTGCTAATGCGGAAGCACTCGACTTTCATGTGACAGAAAGAGGAATGA CG SEQ ID NO 13 IU DU Og MKLKSKLFVICLAAAAIFTAAGVSANAEALDFHVTERGMT SEQ ID NO 14 HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH TTGATCATGACACAACCATCAAAAACTACGAAACTAACTAAAGATGAAGTCGATCGGCT CATAAGCGATTACCAAACAAAGCAAGATGAACAAGCGCAGGAAACGCTTGTGCGGGTG TATACAAATCTGGTTGACATGCTTGCGAAAAAATACTCAAAAGGCAAAAGCTTCCACGA GGATCTCCGCCAGGTCGGCATGATCGGGCTGCTAGGCGCGATTAAGCGATACGATCC TGTTGTCGGCAAATCGTTTGAAGCTTTTGCAATCCCGACAATCATCGGTGAAATTAAAC GTTTCCTCAGAGATAAAACATGGAGCGTTCATGTGCCGAGACGAATTAAAGAACTCGGT CCAAGAATCAAAATGGCGGTTGATCAGCTGACCACTGAAACACAAAGATCGCCGAAAG TCGAAGAGATTGCCGAATTCCTCGATGTTTCTGAAGAAGAGGTTCTTGAAACGATGGAA ATGGGCAAAAGCTATCAAGCCTTATCCGTTGACCACAGCATTGAAGCGGATTCGGACG GAAGCACTGTCACGATTCTTGATATCGTCGGATCACAGGAGGACGGATATGAGCGGGT CAACCAGCAATTGATGCTGCAAAGCGTGCTTC
23. HHHHHHHHHHHHHH HHHHHHHHHHHHHHHH UI subtilisin 50 JP 2007 532114 A 2007 11 15 3 10 HHHHH DU HHHHH HHHHHHHHHHHH 20 30 D HHHHHH
24. 10 20 30 50 2007 532114 A 2007 11 15 10 20 30 50 18 JP 2007 532114 A 2007 11 15
25. 10 20 30 50 85 JP 2007 532114 A 2007 11 15 T o O 7 THUA p7ODR _ non TACACGTTAGAAGACGGCTAGATGCGTCTGATTGTGACAGAC 176 P82 DF GGCG p98spcF Bbsl CCTTGTCTTGAAGACGGAGCTGGATCCATAACTTCGTATAATG p106 spcR Bbsl _ GTACCATAAGAAGACGGCTAGAGGATGCATATGGCGGCCGC p112 UF CATATGCTCCGGCTCTTCAAGCAAG analytical primer 10 RO tdh kbl CTCAGTTCATCCATCAAATCACCAAGTCCG AACCTTCCAGTCCGGTTTACTGTCGC GTACCATAAGAAGACGGAGCTTGCCGTGTCCACTCCGATTAT 178 AGCAG 20 C CTGAGATTGATAAACATGAAGTCCTC analytical primer PCR VD HDH DE O D OO OO 00000 00000 oaaao ATATTGAAGTCGGCTGGATIGTGG 183 SeDUR Bali GCGGCAGATCTCGGCGCATTARGTC
26. 10 20 30 50 JP 2007 532114 A 2007 11 15 34 10 20 10000000 HHHHH 10 D 000000 30 D 50 nnnnnnn HHHHHHHHHHHH
27. 10 20 30 51 JP 2007 532114 A 2007 11 15 TIGTTAACAGCCTTAAAAACAGATACAG GAAAAATCCGCCAGCATAATGAAGATGATG CGGGGATATTCAAGGGGAAAGATGAATTTATATTAGCGGTTGTCG CTGATGGCATGG GCGGCCATCTTGCTGGAGATGTTGCGAGCAAGATGGCTGTGAAAGCCATGGGGGAG AAATGGAATGAAGCAGAGACGATTCCAACTGCGCCCTCG GAATGTGAAAAATGGCTC ATTGAACAGATTCTATCGGTAAACAGCAAAATATACGATCACGCTCAAGCCCACGAAG AATGCCAAGGCATGGGGACGACGATTGTATGTGCACTTTTTACGGG GAAAACGGTTT CTGTTGCCCATATCGGAGACAGCAGATGCTATTTGCTTCAG GACGATGATTTCGTTCA AGTGACAGAAGACCATTCGCTTGTAAATGAACTGGTTCGCACTG GAGAGATTTCCAG AGAAGACGCTGAACATCATCCGCGAAAAAATGTGTTGACGAAGGCGCTTGGAACAGA 10 CCAGTTAGTCAGTATTGACACCCGTTCCTTTGATATAGAACCCGGAGACAAACTGCTT CTATGTTCTGACGGACTGACAAATAAAGTGGAAGGCACTGAGTTAAAAGACATCCTG CAAAGCGATTCAGCTCCTCAGGAAAAAGTAAACCTG CTTGTGGACAAAGCCAATCAG AATGGCGGAGAAGACAACATTACAGCAGTTTTGCTTGAGCTTGCTTTACAAGTTGAAG AGGGTGAAGATCAGTGC SEQ ID NO 29 MLTALKTDTGKIRQHNEDDAGIFKGKDEFILAVVADGMGGHLAGDVASKMAVKAMGEKW 20 NEAETIPTAPSECEKWLIEQILSVNSKIYDHAQAHEECQGMGTTIVCALFTGKTVSVAH IG OSRCYLLQDDDFVQVTEDHSLVNELVRTGEISREDAEHHPRKNVLTKALGTDQLVSIDTR SFDIEPGDKLLLCSDGLTNKVEGTELKDILQSDSAPQEKVNLLVDKANQNGGEDNITAVLL ELALQVEEGEDQC SEQ ID NO 30
28. HHHHHHHHHH 50 DU H H HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH
29. 10 20 30 81 JP 2007 532114 A 2007 11 15 7 DHB UF CGAGAATCTAGAACAGGATGAATCATCTGTGGCGGG DHB UFfus phleo BamHi CGACTGTCCAGCCGCTCGGCACATCGGATCCGCTTA 111 f P CCGAAAGCCAGACTCAGCAA DHB URfus phleo BamHI TTGCTGAGTCTGGCTTTCGGTAAGCGGATCCGATGIG 112 I CCGAGCGGCTGGACAGTCG DHB DFfus phleo CGTTAATGCGCCATGACAGCCATGAGGATCCCACAA GCCCGCACGCCTTGCCACAC GACTTCGTCGACGAGTGCGGACGGCCAGCATCACCA 115 GGCATATCTAGAGACAT GAAGCGGGAAACAGATG GGTGCGGAGCTCGACAGTATCACAGCCAGCGCTG AAGCGTTCTAGACTGCGGATGCAGATCGATCTCGGG YvfF yveK UF BamHI AACCTTCCGCTCACATGTGAGCAGGGGATCC 119 phleo GCTTACCGAAAGCCAGACTCAGCAA YvfF yveK UR BamHI TIGCTGAGTCTGGCTTTCGGTAAGCGGATCC 120 phleo CCTGCTCACATGTGAGCGGAAGGTT YvfF yveK DF BamHI CGTTAATGCGCCATGACAGCCATGAGGATCC 124 phleo GCCTTCAGCCTTCCCGCGGCTGGCT YviF yveK DR BamHI AGCCAGCCGCGGGAAGGCTGAAGGCGGATCC 122 phleo TCATGGCTGTCATGGCGCATTAACG YvfF yveK DR Pst CAAGCACTGCAGCCCACACTTCAGGCGGCTCAGGTC 123 YvfF yveK UF GAGATATCTAGAATGGTATGAAGCGGAATTCCCG 124 123 124 ATAAACGGTACCCCCCTATAGATGCGAACGTTAGCCC 7 1774 TUF EcoRI AAGGAGGAATTCCATCTTGAGGTATACAAACAGT CAT 127 128 9 131
30. JP 2007 532114 A 2007 11 15 35 ERTZ D 00 Uu 10 20 30 HHHHHHHHHHHHHHHHHHH DU 50
31. JP 2007 532114 A 2007 11 15 6 10 20 30 50 000 JOD HHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH
32. 50 22 JP 2007 532114 A 2007 11 15
33. UI GTGATCACAAGAGATTTTTTCTTATITITATCCAAAAGCGGCTTTCTCAATAAAATGGC GAGGAACTGGGGAAGTCGGGTAGCAGCGGGTAAAATTATCGGCGGGAATGACTTTA ACAGTTCAATCCCGACCATTCGACAGCTTAACAGCCAAGGCTTGTCAGTTACTGTCGA TCATTTAGGCGAGTTTGTGAACAGCGCCGAGGTCGCACGGGAGCGTACGGAAGAGT GCATTCAAACCATTGCGACCATCGCGGATCAGGAGCTGAACTCACACGTTTCTTTAAA AATGACGTCTTTAGGTTTGGATATAGATATGGATTTGGTGTATGAAAATATGACAAAAA TCCTTCAGACGGCCGAGAAACATAAAATCATGGTCACCATTGACATGGAGGACGAAG TCAGATGCCAGAAAACGCTTGATATTTTCAAAGATTTCAGAAAGAAATACGAGCATGT GAGCACAGTGCTGCAAGCCTATCTGTACCGGACGGAAAAAGACATTGACGATTTGGA TTCTTTAAACCCGTTCCTTCGCCTTGTAAAAGGAGCTTATAAAGAATCAGAAAAAGTA GCTTTCCCGGAGAAAAGCGATGTCGATGAAAATTACAAAAAAATCATCCGAAAGCAG CTCTTAAACGGTCACTATACAGCGATTGCCACACATGACGACAAAATGATCGACTTTA CAAAGCAGCTTGCCAAGGAACATGGCATTGCCAATGACAAGTTTGAATTTCAGATGCT GTACGGCATGCGGTCGCAAACCCAGCTCAGCCTCGTAAAAGAAGGTTATAACATGAG AGTCTACCTGCCATACGGCGAGGATTGGTACGGCTACTTTATGAGACGCCTTGCAGA l ACGTCCGTCAAACATTGCATTTGCTTTCAAAGGAATGACAAAGAAG SEQ ID NO 52 10000 HHHHHHHHHHHHHHHHHHH mu 10 20 30 40 60 JP 2007 532114 A 2007 11 15 00000 MITRDFFLFLSKSGFLNKMARNWGSRVAAGKIIGGNDFNSSIPTIRQLNSQGLSVTVDHL GEFVNSAEVARERTEECIQTIATIADQELNSHVSLKMTSLGLDIDMDLVYENMTKILQTA EKHKIMVTIDMEDEVRCQKTLDIFKDFRKKYEHVSTVLQAYLYRTEKDIDDLDSLNPFLR LVKGAYKESEKVAFPEKSDVDENYKKIIRKQLLNGHYTAIATHDDKMIDFTKQLAKEHGI ANDKFEFOMLY
34. DU JP 2007 532114 A 2007 11 15 71 IOOOOOO 1 Uu 10 20 30 D
35. 10 20 30 50 84 JP 2007 532114 A 2007 11 15 K5 PckA 7 1 None TITGCTTICCTCCTGCACAAGGCCTC EEE hen PCK 2 None CGTTATTGTGTGTGCATTTCCATTGT E ORR NL 3 None GAGA 201 E ue Fa PCK 4 GTAATGGCCCTCTCGTATAAAAAAC 202 203 04 Ta PA GTTTITTATACGAGAGGGCCATTACCAATTAGAAT Pi 5 o None GAATATTTCCC F PNE PE 6 None GACCAAAATGTTTCGATTCAGCATTCCT 2
36. O n HHHHHHHHHHHH 50 IlHHHHHH D OO JP 2007 532114 A 2007 11 15 9 10 20 30 HHHHHHHHHHH
37. B mm 0 0 0 10 20 30 50 27 JP 2007 532114 A 2007 11 15 10 20 30 50 JP 2007 532114 A 2007 11 15 28 10
38. SIE 11 Eg E OOO ZI 0 Li EI EE EI El EX EIE Li EA EE EO sl E ET ETE OOO 0 0 10 20 30 56 JP 2007 532114 A 2007 11 15 O0 TAATACGATAAGAACAGCTTAGAAATACACAAGAGTGTGTATAAAGCAATTAGAATGA GTTGAGTTAGAGAATAGGGTAGCAGAGAATGAGTTTAGTTGAGCTGAGACATTATGTT TATTCTACCCAAAAGAAGTCTTTCTTTTGGGITTATTTGTTATATAGTATTTTATCCTCT CATGCCATCTTCTCATTCTCCTTGCCATAAGGAGTGAGAGCAATGAATTTCCAATCAA ACATTTCCGCATTTTTAGAGGACAGCTTGTCCCACCACACGATACCGATTGTGGAGAC CTTCACAGTCGATACACTGACACCCATTCAAATGATAGAGAAGCTTGACAGGGAGATT ACGTATCTTCTTGAAAGCAAGGACGATACATCCACTTGGTCCAGATATTCGTTTATCG GCCTGAATCCATTTCTCACAATTAAAGAAGAGCAGGGCCGTTTTTCGGCCGCTGATC AGGACAGCAAATCTCTTTACACAGGAAATGAACTAAAAGAAGTGCTGAACTGGATGAA TACCACATACAAAATCAAAACACCTGAGCTTGGCATTCCTTTTGTCGGCGGAGCTGTC GGGTACTTAAGCTATGATATGATCCCGCTGATTGAGCCTTCTGTTCCTTCGCATACCA AAGAAACAGACATGGAAAAGTGTATGCTGTTTGTTTGCCGGACATTAATTGCGTATGA TCATGAAACCAAAAACGTCCACTTTATCCAATATGCAAGGCTCACTGGAGAGGAAACA AAAAACGAAAAAATGGATGTATTCCATCAAAATCATCTGGAGCTTCAAAATCTCATTGA AAAAATGATGGACCAAAAAAACATAAAAGAGCTGTTTCTTTCTGCTGATTCATACAAGA CACCCAGCTTTGAGACAGTATCTTCTAATTATGAAAAATCGGCTTTTATGGCTGATGTA GAAAAAATCAAAAGCTATATAAAAGCAGGCGATATCTTCCAGGGTGTTTTATCACAAA AATTTGAGGTGCCGATAAAAGCAGATGCTTTTGAGTTATACCGAGTGCTTAGGATCGT CAATCCTTCGCCGTATATGTATTATATGAA
39. HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 33 JP 2007 532114 A 2007 11 B DE
40. JP 2007 532114 A 2007 11 15 36 10 20 30 HHHHHHHHHHHHHHH 50 DU OO 00 O HHHHH HHHHHHHHHHHH 37 JP
41. 0000000 JP 2007 532114 A 2007 11 15 32 40 20 D D D D 00000 50
42. KOI 7L NaH2PO4 H2O 0 8 56g KH2PO4 0 8 56g MgSO4 7H20 0 28 19 69 0 1 Tg CaCI2 2H20 0 01 0 79 71120 0 03 2 19 MnCI2 4H20 0 02 1 4g 100 x 1 70g H2S04 0 16 11 2g 60967 jv 3 A 1 29 90 549 U DU TOO JP 2007 532114 A 2007 11 15 92 10 20
43. H O MKRESNIQVLSRGQKDQPVSQIYQVSTMTSLLDGVYDGDF ELSEIPKYGDFGIGTFNKLD GELIGFDG EFYRLRSDGTATPVQNGDRSPFCSFTFFTPDMTHKIDAKMTREDFEKEINSM LPSRNLFYAIRIDGLFKKVOTRTVELOEKPYVPMVEAVKTOPIFNFDNVRGTIVGFLTPAYA NGIAVSGYHLHFIDEGRNSGGHVFDYVLEDCTVTISOKMNMNLRLPNTADFFNANLDNPD FAKDIETTEGSPE SEQ ID NO 22 zu n HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH n n n o O 10 20 30 50 48 JP 2007 532114 A 2007 11 15 ATGAAGGTAAAAGTAGCGATCAACGGGTTTGGAAGAATCGGAAGAATGGTTTTTAGA AAAGCGATGTTAGACGATCAAATTCAAGTAGTGGCCATTAACGCCAGCTATTCCGCA GAAACGCTGGCTCATTTAATAAAGTATGACACAATTCACGGCAGATACGACAAAGAG GTTGTGGCTGGTGAAGATAGCCTGATCGTAAATGGAAAGAAAGTGCTTTTGTTAAACA GCCGTGATCCAAAACAGCTGCCTTGGCGGGAATATGATATTGACATAGTCGTCGAAG CAACAGGGAAGTTTAATGCTAAAGATAAAGCGATGGGCCATATAGAAGCAGGTGCAA AAAAAGTGATTTTGACCGCTCCGGGAAAAAATGAAGACGTTACCATTGTGATGGGCG TAAATGAGGACCAATTCGACGCTGAGCGCCATGTCATTATTTCAAATGCGTCATGCAC GACAAATTGCCTTGCGCCTGTTGTAAAAGTGCTGGATGAAGAGTTTGGCATTGAGAG 10 CGGTCTGATGACTACAGTT CATGCGTATACGAATGACCAAAAAAATATTGATAACCCG CACAAAGATTTGCGCCGGGCGCGGGCTTGCGGTGAATCCATCATTCCAACAACAACA GGAGCGGCAAAGGCGCTTTCGCTTGTGCTGCCGCATCTGAAAGGAAAACTTCACGG CCTCGCCTTGCGTGTC
44. 10 20 30 50 2007 532114 A 2007 11 15 10 20 30 50 JP 2007 532114 A 2007 11 15 66 10 20 30 JO
45. 7 5 T UF TCTCCGAGAAAGACAGGCAGGATCGGGATCC 127 7 077 TUR BamHI TTGCTGAGTCTGGCTTTCGGTAAGCGGATCC 128 E EAT SO zd 7 AAGGACGGTACCGGCTCATTACCCTCTTTTCAAGGG 3 Asp718 phieo pro7 UR BamHI TTGCTGAGTCTGGCTTTCGGTAAGCGGATCC phieo TCTCGCGGGGGAGTCCGGCTTTGGT pro7 DF BamHi CGTTAATGCGCCATGACAGCCATGA 132 phieo GGATCCCATACGGGGTACACAATGTACCATA pro7 DR BamHi TATGGTACATTGTGTACCCCGTATGGGATCC 133 phleo TCATGGCTGTCATGGCGCATTAACG Bim pro7 DR Psu GTCAACCTGCAGAGCGGCCCAGGTACAAGTTGGGGA pro7 UF Sact GGATCAGAGCTCGCTTGTCCTCCTGGGAACAGCCGG pro7 DR Psl TATATGCTGCAGGGCTCAGACGGTACCGGTTGTTCCT ii Xbal TCTAGA BamHI GGATCC Sacl GAGCTC Asp718 GGTACC PstI CTGCAG HindIII AAGCTT m pro7 UF ACCAAAGCCGG ACTCCCCCGCGAGAGGATCC 130 GCTTACCGAAAGCCAGACTCAGCAA HHHHHH DHB DRfus phleo BamHI GTGTGGCAAGGCGTGCGGGCTTGTGGGATCCTCATG 114 GCTGTCATGGCGCATTAACG f 10 20 30 50 82 JP 2007 532114 A 2007 11 15 KA PCR Sir UF CTGAACTCTAGACCTTCACCAGGCA
46. a D EL BN ZE DK JA DN OD 0000060 MYPYPNEIGRYGDFGGKFVPETLMQPLDEIQTAFKQIKDDPAFREEYYKLLKDYSGRPTA LTYADRVTEYLGGAKIYLKREDLNHTGSHKINNALGQALLAKKMGKTKIIAETGAGQHGVA AATVAAKFGFSCTVFMGEEDVARQSLNVFRMKLLGAEVVPVTSGNGTLKDATNEAIRYW VQHCEDHFYMIGSVVGPHPYPQVVREFQKMIGEEAKDQLKRIEGTMPDKVVACVGGGS NAMGMFQAFLNEDVELIGAEAAGKGIDTPLHAATISKGTVGVIHGSLTYLIQDEFGQIIEPY SISAGLDYPGIGPEHAYLHKSGRVTYDSITDEEAVDALKLLSEKEGILPAIESAHALAKAFKL AKGMDRGQLILVCLSGRGDKDVNTLMNVLEEEVKAHV SEQ ID NO 43 100000 VIOOOAOOOOAODOOO O AOOOAODOOAODOORODOOOODOOIR MLEKIIKQKKEEVKTLVLPVEQPFEKRSFKEAPASPNRFIGLIAEVKKASPSKGLIKEDF VPVQIAKDYEAAKADAISVLTDTPFFQGENSYLSDVKRAVSIPVLRKDFIIDSLQVEESR RIGADAILLIGEVLDPLHLHELYLEAGEKGMDVLVEVHDASTLEQILKVFTPDILGVNNR NLKTFETSVKQTEQIASLVPKESLLVSESGIGSLEHLTFVNEHGARAVLIGESLMRQTSQ RKAIHALFRE SEQ ID NO 45 NOD DU E D 1000000 T T n 000000 DO MNRFLQLCVDGKTLTAGEAETLMNMMMAAEMTPSEMGGILSILAHRGETPEELAGFVKA MRAHALTVDGLPDIVDTCGTGGDGISTFNISTASAIVASAAGAKIAKHGNRSVSSKSGSAD VLEELEVSIQTTPEKVKSSIETNNMGFLFAPLYHSSMKHVAGTRKELGFRTVFNLLGPLSN PLQAKRQVIGVYSVEKAGLMASALETFQPKHVMFVSSRDGLDELSITAPTDVIELKDGER REY TVSPEDFGFTNGRLEDLQVQSP
47. 10 20 30 62 JP 2007 532114 A 2007 11 15 10 20 30 50 63 JP 2007 532114 A 2007 11 15
48. OD ONG GN DDD O O A nnnnnAnnn EIE EE EE ESEL EE EE DE Ee Ge arka AE eet OE BE ET EE OE gt iE EN n EE E M Hera EN Hi EEE 94 JP 2007 532114 A 2007 11 15 O d C park aren kal er gC Olo 3 E 7 n74Y
49. A HN IN DAE ANA 10 20 30 53 JP 2007 532114 A 2007 11 15 IU IU DU ATGACAGCTTTATCTAAATCCAAAGAAATTATTGATCAGACGTCTCATTACGGAGCCA ACAATTATCACCCGCTCCCGATTGTTATTTCTGAAGCGCTGGGTGCTTGGGTAAAGG ACCCGGAAGGCAATGAATATATGGATATGCTGAGTGCTTACTCTGCGGTAAACCAGG GGCACAGACACCCGAAAATCATTCAGGCATTAAAGGATCAGGCTGATAAAATCACCC TCACGTCACGCGCGTTTCATAACGATCAGCTTGGGCCGTTTTACGAAAAAACAGCTAA ACTGACAGGCAAAGAGATGATTCTGCCGATGAATACAGGAGCCGAAGCGGTTGAATC CGCGGTGAAAGCGGCGAGACGCTGGGCGTATGAAGTGAAGGGCGTAGCTGACAAT CAAGCGGAAATTATCGCATGTGTCGGGAACTTCCACGGCCGCACGATGCTGGCGGT ATCTCTTTCTTCTGAAGAGGAATATAAACGAGGATTCGGCCCGATGCTTCCAGGAATC 10 AAACTCATTCCTTACGGCGATGTGGAAGCGCTTCGACAGGCCATTACGCCGAATACA GCGGCATTCTTGTTTGAACCGATTCAAGGCGAAGCGGGCATTGTGATTCCGCCTGAA GGATTTTTACAGGAAGCGGCGGCGATTTGTAAGGAAGAGAATGTCTTGTTTATTGCG GATGAAATTCAGACGGGTCTCGGACGTACAGGCAAGACGTTTGCCTGTGACTGGGA CGGCATTGTTCCGGATATGTATATCTTGGGCAAAGCGCTIGGCGGCGGTGTGTTCCC GATCTCTTGCATTGCGGCGGACCGCGAGATCCTAGGCGTGTTTAACCCTGGCTCACA CGGCTCAACATTTGGTGGAAACCCGCTTGCATGTGCAGTGTCTATCGCTTCATTAGAA GTGCTGGAGGATGAAAAGCTGGCGGATCGTTCTCTTGAACTTGGTGAATACTTTAAA AGCGAGCTTGAGAGTATTGACAGCCCTGTCATTAAAGAAGTCCGCGGCAGAGGGCT GTTTATCGGTGTGGAATT GACT GAAGCGGCACGTCCGTATTGTGAGCGTTTGAAGGA AGAGGGACTTTTATGCAAGGAAACGCATGATACAGTCATTCGTTTTGCACCGCCATTA ATCATITCCAAAGAGGACTTGGATTGGGCGATAGAGAAAATTAAGCACGTGCTG
50. L1 DI 00 BA JN OIR OOOO MAH 30 CJ 52 JP 2007 532114 A 2007 11 15 00000 ATGACAGTCACATACGCGCACGAACCATTTACCGATTTTACGGAAGCAAAGAATAAAA CTGCATTTGGGGAGTCATTGGCCTITGTAAACACTCAGCTCGGCAAGCATTATCCGC TTGTCATAAATGGAGAAAAAATTGAAACGGACCGCAAAATCATTTCTATTAACCCGGC AAATAAAGAAGAGATCATTGGGTACGCGTCTACAGCGGATCAAGAGCTTGCTGAAAA AGCGATGCAAGCCGCATTGCAGGCATTTGATTCCTGGAAAAAACAAAGACCGGAGCA CCGCGCAAATATTCTCTTTAAGGCAGCGGCTATTTTGCGCAGAAGAAAGCATGAATTT TCAAGCTATCTTGTGAAGGAAGCAGGAAAACCGTGGAAGGAAGCAGATGCGGACAC GGCTGAAGCGATAGACTTTTTAGAGTTCTACGCGCGCCAAATGTTAAAGCTCAAGGA AGGGGCTCCGGTGAAGAGCCGTGCTGGCGAGGTCAATCAATATCATTACGAAGCGC TTFGGCGTCGGCATCGTCATTTCTCCATTTAACTTCCCGCTCGCGATTATGGCGGGAA CAGCGGTGGCAGCGATTGTGACAGGAAATACGATTCTCTTAAAACCGGCTGACGCAG CCCCGGTAGTGGCAGCAAAATTTGTCGAGGTCATGGAGGAAGCGGGTCTGCCAAAC GGCGTTCTGAATTACATTCCGGGAGATGGTGCGGAGATCGGTGATTTCTTAGTTGAG CATCCGAAGACACGGTTTGTCTCATTTACAGGTTCCCGTGCAGTCGGCTGCCGGATT TATGAGCGAGCTGCCAAAGTGCAGCCGGGCCAAAAATGGCTCAAACGGGTAATTGC AGAAATGGGCGGAAAAGACACAGTGCTTGTCGACAAGGACGCTGATCTTGACCTTGC TGCATCCTCTATCGTGTATTCAGCATTTGGATATTCAGGACAGAAGTGTTCTGCGGGC TCCCGCGCGGTCATTCATCAGGATGTGTATGATGAAGTGGTGGAAAAAGCTGTGGCG CTGACCAAAACGCTGACTGTCGGC
51. CJ DI DI DI DI CJ DI rd 00000 D EL EI RN D TIGAGGATGAAGCAGACGATTCCGTCCTCTTATGTCGGGCTTAAAATTAATGAATGGTA TACTCATATCCGGCAGTTCCACGTCGCTGAAGCCGAACGGGTCAAGCTCGAAGTAGAA AGAGAAATTGAGGATATGGAAGAAGACCAAGATTTGCTGCTGTATTATTCTTTAATGGA GTTCAGGCACCGTGTCATGCTGGATTACATTAAGCCTTTTGGAGAGGACACGTCGCAG CTAGAGTTTTCAGAATTGTTAGAAGACATCGAAGGGAATCAGTACAAGCTGACAGGGCT TCTCGAATATTACTTTAATTTTTTTCGAGGAATGTATGAATTTAAGCAGAAGATGTTTGTOC AGTGCCATGATGTATTATAAACGGGCAGAAAAGAATCTTGCCCTCGTCTCGGATGATAT TGAGAAAGCAGAGTTTGCTTTTAAAATGGCTGAGATTTTTTACAATTTAAAACAAACCTA TGTTTCGATGAGCTACGCCGTTCAGGCATTAGAAACATACCAAATGTATGAAACGTACA CCGTCCGCAGAATCCAATGTGAATTCGTTATTGCAGGTAATTATGATGATATGCAGTAT CCAGAAAGAGCATTGCCCCACTTAGAACTGGCTTTAGATCTTGCAAAGAAAGAAGGCA ATCCCCGCCTGATCAGTTCTGCCCTATATAATCTCGGAAACTGCTATGAGAAAATGGGT GAACTGCAAAAGGCAGCCGAATACTTTGGGAAATCTGTTTCTATTTGCAAGTCGGAAAA GTTCGATAATCTTCCGCATTCTATCTACTCTTTAACACAAGTTCTGTATAAACAAAAAAAT GACGCCGAAGCGCAAAAAAAGTATCGTGAAGGATTGGAAATCGCCCGTCAATACAGTG ATGAATTATTTGTGGAGCTTTTTCAATTTTTACATGCGTTATACGGAAAAAACATTGACA CAGAATCAGTCTCACACACCTTTCAATTTCTTGAAGAACATATGCTGTATCCTTATATTG AAGAGCTGGCGCATGATGCTGCCCAATTCTATATAGAAAACGGACAGCCCGAAAAAGC ACTTTCATTTTATGAGAAAATGGTGCACGCACAAAAACAAATCCAGAGAGGAGATTGTT TATATGAAATC SEQ ID NO 15
52. 10 20 30 50 79 JP 2007 532114 A 2007 11 15 G 10 20 C mM 1 m m F1 MM mam m m 30 80 JP 2007 532114 A 2007 11 15 KO EBRIO OS RAIDS pc c bo Ir Csn
53. IU 20 30 50 JP 2007 532114 A 2007 11 15 39 10 20 30 50 HHHHHHHHHHHHHHHHHHHHHHHHHHH
54. ATGCAATCCTTGAATTATGAAGATCAGGTGCTTTGGACGCGCTGGAAAGAGTGGAAA GATCCTAAAGCCGGTGACGACTTAATGCGCCGTTACATGCCGCTTGTCACATATCAT GTAGGCAGAATTTCTGTCGGACTGCCGAAATCAGTGCATAAAGACGATCTTATGAGC CTTGGTATGCTTGGTTTATATGATGCCCTTGAAAAATTTGACCCCAGCCGGGACTTAA AATTTGATACCTACGCCTCGTTTAGAATTCGCGGCGCAATCATAGACGGGCTTCGTAA AGAAGATTGGCTGCCCAGAACCTCGCGCGAAAAAACAAAAAAGGTTGAAGCAGCAAT TGAAAAGCTTGAACAGCGGTATCTTCGGAATGTATCGCCCGCGGAAATTGCAGAGGA ACTCGGAATGACGGTACAGGATGTCGTGTCAACAATGAATGAAGGTTTTTTTGCAAAT CTGCTGTCAATTGATGAAAAGCTCCATGATCAAGATGACGGGGAAAACATTCAAGTCA TGATCAGAGATGACAAAAATGTTCCGCCTGAAGAAAAGATTATGAAGGATGAACTGAT TGCACAGCTTGCGGAAAAAATTCACGAACTCTCTGAAAAAGAACAGCTGGTTGTCAG TTTGTTCTACAAAGAGGAGTTGACACTGACAGAAATCGGACAAGTATTAAATCTTTCT ACGTCCCGCATATCTCAGATCCATTCAAAGGCATTATTTAAATTAAAGAATCTGCTGG AAAAAGTGATACAA SEQ ID NO 56 Dr HHHHHHHHHHHHHHH MQSLNYEDQVLWTRWKEWKDPKAGDDLMRRYMPLVTYHVGRISVGLPKSVHKDDLMS LGMLGLYDALEKFDPSRDEKFDTYASFRIRGAIIDGLRKEDWLPRTSREKTKKVEAAIEKL EQRYLRNVSPAEIAEELGMTVQDVVSTMNEGFFANLLSIDEKLHDQDDGENIQVMIRDDK NVPPEEKIMKDELIAQLAEKIHELSEKEQLVVSLFYKEELTLTEIGQVLNLSTSRISQIHSKA LFKLKNLLEKVIQ SEQ ID NO 57 HHHHHHHHHHHHHHHHHHHHHHHHHHHHH
55. C C C Aa A Ah TI TI TI na or Aa A TI OO TI ra N nnna C JP 2007 532114 A 2007 11 15 31 C 10 20 30 10000000 D
56. JP 2007 532114 A 2007 11 15 25 10 20 O 000 o O 30 O 10000000 IU HHHHH OD DU 50 26 JP 2007 532114 A 2007 11 15
57. 54 pckA 590000 0000000000000 000000000 HHHHHHHHHHHHHHHHHHHHHHHHH ER aou apaspa HHHHHHHHHHHHHHHHHHHHHHHHH 0000000000000000000000000 EEE F 1000 1000 100000000 1000 100 100000000 re 1000 100 100000000 SN 1000 J0000000000000000 su sam 10000000000 100000000 d 10000000000 100000000 1000 1000 1000 JP 2007 532114 A 2007 11 15 2 U D 40 20 EE EP TEN EN EN Uu Bacillus subtili s B IOOOOOO HHHHH 30
58. HHHHHH 45 JP 2007 532114 A 2007 11 15 MRMKQTIPSSYVGLKINEWYTHIRQFHVAEAERVKLEVEREIEDMEEDQDLLLYYSLMEF RHRVMLDYIKPFGEDTSQLEFSELLEDIEGNQYKLTGLLEYYFNFFRGMYEFKQKMFVSA MMYYKRAEKNLALVSDDIEKAEFAFKMAEIFYNLKQTYVSMSYAVQALETYQMYETYTVR RIQCEFVIAGNY DDMQYPERALPHLELALDLAKKEGNPRLISSALYNLGNCYEKMGELQK AAEYFGKSVSICKSEKFDNLPHSIYSLTQVLYKQKNDAEAQKKYREGLEIARQYSDELFVE LFQFLHALYGKNIDTESVSHTFQFLEEHMLYPYIEELAHDAAQFYIENGQPEKALSFYEKM VHAQKQIQRGDCLYEI SEQ ID NO 16 A ER Aa da 8 DI CJ CJ EI n r1 HHHHHHHHHHHHHHHH ATGAAAAACAAGCCGCTCGCGTTTCAGATATGGGTTGTCATATCCGGCATCCTGTTAG CGATATCGATTTTACTGCTTGTGTTATTTTCAAACACGCTGCGAGATTTTTTCACTAAT GAAACGTATACGACGATTGAAAATGAGCAGCATGTTCTGACAGAGTACCGCCTGCCA GGTTCGATTGAAAGGCGCTATTACAGCGAGGAAGCGACGGCGCCGACAACTGTCCG CTCCGTACAGCACGTGCTCCTTCCTGAAAATGAAGAGGCTTCTTCAGACAAGGATTTA AGCATTCTGTCATCTTCATTTATCCACAAGGTGTACAAGCTGGCTGATAAGCAGGAAG CTAAAAAGAAACGTTACAGCGCCGACGTCAATGGAGAGAAAGTGTTTTTTGTCATTAA AAAGGGACTTTCCGTCAATGGACAATCAGCGATGATGCTCTCTTACGCGCTTGATTCT TATCGGGACGATTTGGCCTATACCTTGTTCAAACAGCTTCTGTTTATTATAGCTGTCGT CATTTTATTAAGCTGGATTCCGGCTATTTGGCTTGCAAAGTATTTATCA
59. D 30 HHHHH HHHHHHHHHH O 10000000 D Uu DU IU 50
60. BamHI D sam FRED 1 sk BamHI BamHI 1 RE1 2 RE2 BamHI pe m ape diee PTMI02 uie u o 5mL q nun s El 1A 1B 96 JP 2007 532114 A 2007 11 15 4 5 2 NON U RAR t D BamHI BamHI Se 1 RE 4 i 4 RHR 2 RE2 y EA U D 3 Bd 5 Ed 6 JP 2007 532114 A 2007 11 15 97 N s L Bra ELA Baga MINA ELAS SNE co ST ST SE sp VV WHA ALLL 819 Gia Lda X _pyod WEE n Vaky COT Bg 007 oor 009 008 000 0021 TO qO ME D aK E BS E nu n 50 EPT 98 JP 2007 532114 A 2007 11 15 X 10 C EPT 99 JP 2007 532114 A 2007 11 15 60700160019
61. 20 30 50 o O HHHHHHHHHHHHHHHHHHHHHH 29 JP 2007 532114 A 2007 11 15
62. II NTRNATIONAL SEARCH REPORT PCT US2005 011821 According to Intemational Patent Classificallon IPO or to both national classification and PC B FIELDS SEARCHED Minimum documanietion seerchad classification system followed by classification symbols CO7K C12R CI2N Documentation searched other than minimum documentation to tha extent that such documents are Included In tha fields searched Electronic dala base consulled during the International search nama of dala base and where practical search terms used EPO Internal WPI Data PAJ MEDLINE Sequence Search BIOSIS TNV CO7K14 32 CLNIS 63 C12N9 88 ADD C12R1 125 C DOCUMENTS CONSIDERED TO BE RELEVANT Citation of documant with indication where appropriate of the relayant passages WO 03 083125 A GENENCOR INTERNATIONAL INC FERRARI EUGENIO HARBISON CAROLE RASHI 9 Octaber 2003 2003 10 09 the whole document in particular p 86 1 1 15 and claims US 2002 065403 A1 EIKMANNS BERNHARD ET AL 30 May 2002 2002 05 30 the whole document in particular Example 5 x Further documents are listed In the continuation of Box C Special catagories of cited documents a era akan ta ana A document defining tha state of the ait which Is not a P rga Garakoi ganeral sisio of th cited to understand the principle or theory underying the E earfier document but published on or after the Intemational X document of part
63. ize 1 27 38 44 55 64 The additional search faes were accompanied by the applicant s protest L No protest accompanied the payment of additional search feas Form PCT ISA 210 continuation of first sheet 2 January 2004 101 JP 2007 532114 A 2007 11 15 Intemational Application No PCT US2005 011821 FURTHER INFORMATION CONTINUED FROM PCTASA 210 This International Searching Authority found multiple groups of inventions in this international application as follows Inventionl Claims 1 27 38 44 55 64 Microorganisms in particular Bacillus comprising a modified pckA gene methods for enhancing production of a protein by inactivating the pckA gene and methods for obtaining Bacilius subtilis strains having enhanced protease en wherein pckA is deleted in the chromosome of said strains Inventions 2 28 claims 28 37 all partially Isolated nucleic acids SEQ ID NOs 1 3 5 7 9 11 13 15 39 40 42 44 46 48 50 37 25 21 50 23 2 7 19 31 48 46 35 33 corresponding sequences of encoded polypeptides SEQ ID NOs 2 4 6 etc and host cells transformed with said nucleic acids Invention 29 Claims 45 54 Methods for obt fning an altered Bacillus strain expressing protein of interest wherein said Bacillus host cell comprises the pckA gene and has furthermore one or more chromosomal genes inactivated Invention 30 Claims 65 74 Methods for enhancing the expression of a protein of interest in Bacillus wherein
64. CTGGAGTACCTGGATCTGGATCTCC i88 CGGTTTGAGCTCGCGTCCTGATCTGCAGAAGCTCATT 159 59 60 61 1 SigB UF BamHI CTAAAGATGAAGTCGATCGGCTCATGGATCC 1 GCTTACCGAAAGCCAGACTCAGCAA SigB UR BamHi TTGCTGAGTCTGGCTTTCGGTAAGCGGATCC 1 ATGAGCCGATCGACTTCATCTTTAG SigB DF BamHI CGTTAATGCGCCATGACAGCCATGAGGATCC 162 GAAGATCCCTCGATGGAGTTAATGT SigB DR BamHl ACATTAACTCCATCGAGGGATCTTCGGATCC 163 TCATGGCTGTCATGGCGCATTAACG SigB DR Sall GCTTCGGTCGACTTTGCCGTCTGGATATGCGTCTCTCG 7 SigB UF GTCAAAGAGCTCTATGACAGCCTCCTCAAATIGCAGG SigB DR TTCCATGTCGACGCTGTGCAAAACCGCCGGCAGCGCC 68 SpollSA UF ACATTCGAATTCAGCAGGTCAATCAGCTCGCTGACGC 167 SpollSA UF BamHi CCAGCACTGCGCTCCCTCACCCGAAGGATCC 1 GCTTACCGAAAGCCAGACTCAGCAA SpollSA UR TTGCTGAGTCTGGCTTTCGGTAAGCGGATCC TTCGGGTGAGGGAGCGCAGTGCTGG SpollSA DF BamHI CGTTAATGCGCCATGACAGCCATGAGGATCC 170 TCGAGAGATCCGGATGGTTTTCCTG SpoliSA DR BamHI CAGGAAAACCATCCGGATCTCTCGAGGATCC 171 TCATGGCTGTCATGGCGCATTAACG SpollSA OR AGTCAT AAGCTTTCTGGCGTTTGATTTCATCAACGGG 173 174 SpollSA UF CAGCGCGACTTGTTAAGGGACAATA 173 SpollSA DR GGCTGCTGTGATGAACTITGTCGGA 174 phleo ERE d zn
65. 10 GCGCCCGGTCACTTGATGAAGGGGAGCGCAAGTACATTAAGGAAAGCGGCATGAAG GTGTACACAATGCACGAAATCGATCGTCTTGGCATGACAAAGGTCATTGAAGAAACC CTTGATTATTTATCAGCATGTGATGGCGTCCATCTGAGCCTTGATCTGGACGGACTTG ATCCGAACGACGCACCGGGTGTCGGAACCCCTGTCGTCGGCGGCATCAGCTACCGG GAGAGCCATTTGGCTATGGAAATGCTGTATGACGCAGGCATCATTACCTCAGCCGAA TTCGTTGAGGTTAACCCGATCCTTGATCACAAAAACAAAACGGGCAAAACAGCAGTA GAGCTCGTAGAATCCCTGTTAGGGAAGAAGCTGCTG SEQ ID NO 35 DU 0000 20 MDKTISVIGMPMDLGQARRGVDMGPSAIRYAHLIERLSDMGYTVEDLGDIPINREKIKND EELKNLNSVLAGNEKLAQKVNKVIEEKKFPLVLGGDHSIAIGTLAGTAKHYDNLGVIWYD AHGDLNTLETSPSGNIHGMPLAVSLGIGHESLVNLEGYAPKIKPENVVIIGARSLDEGER KYIKESGMKVYTMHEIDRLGMTKVIEETLDYLSACDGVHLSLDLDGLDPNDAPGVGTPVV GGISYRESHLAMEMLYDAGIITSAEFVEVNPILDHKNKTGKTAVELVESLLGKKLL SEQ ID NO 36 55 JP 2007 532114 A 2007 11 15 10000 ATGCAGAGTGGAAAGATGAAAGCTCTAATGAAAAAGGACGGGGCGTTCGGTGCTGT GCTGACTGAAGTTCCCATTCCTGAGATTGATAAACATGAAGTCCTCATAAAAGTGAAA GCCGCTTCCATATGCGGCACGGATGTCCACATTTATAATTGGGATCAATGGGCACGT CAGAGAATCAAAACACCCTATGTTTTCGGCCATGAGTTCAGCG
66. 2007 532114 A 2007 11 15 10 20 30 50 JP 2007 532114 A 2007 11 15 38 10
67. 30 50 75 JP 2007 532114 A 2007 11 15 O LU Es E siga o GEE OE a D D H D 10 20 30 50 76 JP 2007 532114 A 2007 11
68. me woe ga le c T Me soy t le c X g Y o ER 10 20 30 50 95 JP 2007 532114 A 2007 11 15 10 20 y u O e BamHI Bi BamHI
69. reasons 1 L Clalms Nos because they relate to subject matter not required to be searched by this Authority namely 2 Claims Nos because they relate to pans ot the Intemational Appitcation that do not comply with the prescribed requirements to such an extent that no meaningful Intemational Search can be carried out specificaliy a ciems Nos because they are dependent claims and are not drafted In accordance with the second and third sentences of Rule 6 4 a Box IN Observations where unity of invention is lacking Continuation of item 3 of first sheet This Intemational Searching Authority found muitipla inventions in this International application as follows see additional sheet 1 As all required additional search fees were timely paki by the applicant this international Search Report covers all O searchable claims 0 2 O As all searchable claims could be searched without effort justifying an additional fee this Authority did not invite payment of any additional fee 8 As only some of the required additional search fees were timely paki by the applicant this intamational Search Report covers only those clalms for which fees were paid specifically claims Nos E an 4 No required additional search fees were timely paid by the applicant Consequently this International Search Report is x restricted to the invention first mentioned in the claims It Is ea by claims Nos
70. said Bacillus host strain comprises a deletion of an indigenous chromosomal region Invention 31 CTaims 75 81 Methods of enhancing the expression of a protein of interest in Bacillus wherein the nucleic acid for the protein of interest is obtained by transcriptome DNA array analysis Invention 32 Claims 82 85 Methods for enhancing the expression of a protein of interest in Bacillus wherein an altered Bacillus strain is used which comprises a modified gene selected from the group consisting of prpC sigD and tdh kb1 102 JP 2007 532114 A 2007 11 15 Y INTERNATIONAL SEARCH REPORT International application No PCT US2005 011821 Chation of document with indication where appropriate of the relevant passages RIEDEL C ET AL CHARACTERIZATION OF THE PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE Form POTASA 210 oonlinustion second sheet Apr 2008 FROM CORYNEBACTERIUM GLUTAMICUM AND SIGNIFICANCE OF THE ENZYME FOR GROWTH AND AMINO ACID PRODUCTION JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY HORIZON SCIENTIFIC PRESS WYMONDHAM GB vol 3 no 4 2001 pages 573 583 XP001031161 ISSN 1464 1801 the whole document in particular Table 1 and paragraph bridging p p 578 579 EP 0 723 011 B 1311101010 00 1110 3 July 2002 2002 07 03 the whole document in particular the claims US 2004 241831 Al PARK YOUNG HOON ET AL 2 December 2004 2004 12 02 the whole docum
71. 03070963 A 28 08 2003 2003208922 Al 1472347 A2 09 09 2003 03 11 2004 A A A A A _ AA A A A morera Form PCTASA 210 patent family annex April 2006 104 JP 2007 532114 A 2007 11 15 5J Int d 000000000 1000 ve D 80000 AP BWGH GM KE LS MUN NA SD SL SZ TZ UG ZM ZW EN AM AZ BY KG KZ MD RU TJ TM EP AT BE BG CH CY Z CE CK EE ES FI FR GR HJ IE IS IT LT LU MG NL PL PT RO SE SI SK TR OX BF B CF CGA GM GA QN GYM M NE SN TO TG AE AG AL AM AT AU AZ BA BB BG BR BWBY EZ CA CH CN OR QU CZ LE IK DM LZ EG EE EG ES FI OG H MHR HJ IN 5 J P KE KG KM KP KR KZ LG LK LR LS L T LU LV M M My MM MIM NZ NA N NO NZ CM PG PH PL PT RQ RU SC SD SE SG SK SL SM SY 1 TM TN TR TT TZ UA UG US UZ VG W YU ZA MAN 74000 100120145 74000 100138438 9000 uu 1000000000 HHHHHHHHHHHHHHHHHHHHHHHHH D 2 000 II 0U uu 000000000000 HHHHHHHHHHHHHHHHHHHHHHHHHHH ID DO OD 48024 A03 A05 BAI
72. 5 10 BE LET VO Ph O 20 DU DU HHHHHH 30 50 JE JE EV dA E JE n
73. A GOI CAO DAD7 EAO4 GNI9 114 4B050 03 LO2 LLO2 48063 QAO1 Qo URO 525 BA OO 48065 AA19X AATSY AC14 BAO BB03 BB15 BCO2 58003 BCO5 BO6 CA33 al
74. AAGAAGAGGTGAAAGCCCATGTTTAAATTGGATCTTCAAC CATCAGAAAAATTGTTTATCCCGTTTATTACGGCGGGCGATCCAGTTCCTGAGGTTTC GATTGAACTGGCGAAGTCACTCCAAAAAGCAGGCGCCACAGCATTGGAGCTTGGTGT TGCATACTCTGACCCGCTTGCAGACGGTCCGGTGATCCAGCGGGCTTCAAAGCGGG CGCTTGATCAAGGAATGAATATCGTAAAGGCAATCGAATTAGGCGGAGAAATGAAAA AAAACGGAGTGAATATTCCGATTATCCTCTTTACGTATTATAATCCTGTGTTACAATTG AACAAAGAATACTTTTTCGCTTTACTGCGGGAAAATCATATTGACGGTCTGCTTGTTC CGGATCTGCCATTAGAAGAAAGCAACAGCCTICAAGAGGAATGTAAAAGCCATGAGG TGACGTATATTTCTTTAGTTGCGCC GACAAGCGAAAGCCGTTTGAAAACCATTATTGA ACAAGCCGAGGGGTTCGTCTACTGTGTATCTTCTCTGGGTGTGACCGGTGTCCGCAA TGAGTTCAATTCATCCGTGTACCCGTTCATTCGTACTGTGAAGAATCTCAGCACTGTT CCGGTTGCTGTAGGGTTCGGTATATCAAACCGTGAACAGGTCATAAAGATGAATGAA ATTAGTGACGGTGTCGTAGTGGGAAGTGCGCTCGTCAGAAAAATAGAAGAATTAAAG GACCGGCTCATCAGCGCTGAAACGAGAAATCAGGCGCTGCAGGAGTTTGAGGATTA TGCAATGGCGTTTAGCGGCTTGTACAGTITAAAA SEQ ID NO 39 O0 40 20 30 50 58 JP 2007 532114 A 2007 11 15 IU MFKLDLQPSEKLFIPFITAGDPVPEVSIELAKSLQKAGATALELGVAYSDPLADGPVIQR ASKRALDQGMNIVKAIELGGEMKKNGVNIPIILFTYYNPVLQLNKEYFFALLRENHIDGL LVPDLPLEESNSLQEECKSHEVTYISLVAPTSESRLKTIIEQAEGFVYCVSSLGVTGVRN EFNSSVYPFIRTVKNLSTVPVAVGFGISNREQVIKMNEISDGVVVGSALVRKIEELKDRL ISAETRNQALQEFEDYAMAFSGLYSLK SEQ ID NO 41
75. AAGATAATGTTGACGGCTTTGTGATTGATTCATCTGTAAAAGGGTCTAGAG GCGGAACTGGTGTTGCATTTTCTTGGGACTGTGTGCCGGAATATCAG CAGGCGGCTA TTGGTAAACGCTGCTTTATCGCTGGCGGCGTGAATCCGGATAG CATCACACGCCTAT TGAAATGGCAGCCAGAAGGAATTGACCTTGCCAGCG GAATTGAAAAAAACGGACAAA AAGATCAGAATCTGATGAGGCTTTTAGAAGAAAGGATGAACCGATATGTATCCATATC CGAATGAAATAGG CAGATACGGTGATTTTGGCGGAAAGTTTGTTCCGGAAACACTCA TGCAGCCGTTAGATGAAATACAAACAGCATTTAAACAAATCAAG GATGATCCCGCTTT TCGTGAAGAGTATTATAAGCTGTTAAAGGACTATTCCGGACG CCCGACTGCATTAACA TACGCTGATCGAGTCACTGAATACTTAGGCGGCGCGAAAATCTATTTGAAACGAGAA GATTTAAACCATACAGGTTCTCATAAAATCAATAATGCGCTAGGTCAAGCGCTGCTTG CTAAAAAAATGGGCAAAACGAAAATCATTGCTGAAACCGGTGCCGGCCAGCATGGTG TTGCCGCTGCAACAGTTGCAGCCAAATTCGGCTTTTCCTGTACTGTGTTTATGGGTGA AGAGGATGTTGCCCGCCAGTCTCTGAACGTTTTCCGCATGAAGCTTCTTGGAGCGGA GGTAGTGCCTGTAACAAGCGGAAACGGAACATTGAAGGATGCCACAAATGAGGCGA TCCGGTACTGGGTTCAGCATTGTGAGGATCACTTTTATATGATTGGATCAGTTGTCGG CCCGCATCCTTATCCGCAAGTGGTCCGTGAATTTCAAAAAATGATCGGAGAGGAAGC GAAGGATCAGTTGAAACGTATTGAAGGCACTATGCCTGATAAAGTAGTGGCATGTGT AGGCGGAGGAAGCAATGCGATGGGTATGTTTCAGGCATTTTTAAATGAAGATGTTGA ACTGATCGGCGCTGAAGCAGCAGGAAAAGGAATTGATACACCTCTTCATGCCGCCAC TATTTCGAAAGGAACCGTAGGGGTTATTCACGGTTCATTGACTTATCTCATTCAGGAT GAGTTCGGGCAAATTATTGAGCCCTACTCTATTTCAGCCGGTCTCGACTATCCTGGAA TCGGTCCGGAGCATGCATATTTGCATAAAAGCGGCCGTGTCACTTATGACAGTATAA CCGATGAAGAAGCGGTGGATGCATTAAAGCTTTTGTCAGAAAAAGAGGGGATTTTGC CGGCAATCGAATCTGCCCATGCGTTAGCGAAAGCATTCAAACTCGCCAAAGGAATGG ATCGCGGTCAACTCATTCTCGTCTGTTTATCAGGCCGGGGAGACAAGGATGTCAACA CATTAATGAATGTATTGG
76. AATCCAGAAGATCCTGATACGTATATGGGTCCC GTGATTCATGAAGCATCCTACAACAAAGTGATGAAATACATTGAAATCGGCAAATCTG AAGGCAAGCTATTGGCCGGCGGAGAAGGCGATGATTCAAAAGGCTACTTTATTCAGC CGACGATCTTTGCAGATGTTGATGAAAACGCCCGCTTGATGCAGGAAGAAATTTTCG GCCCGGTTGTTGCGATTTGCAAAGCGCGTGATTTCGATCATATGCTGGAGATTGCCA ATAACACGGAATACGGATTAACAGGTGCGCTTCTGACGAAAAACCGTGCGCACATTG AACGGGCGCGCGAGGATTTCCATGTCGGAAACCTATATTTTAACAGAGGATGTACCG GAGCAATTGTCGGCTATCAGCCGTTCGGCGGTTTTAATATGTCAGGAACAGACTCAA AAGCAGGCGGTCCCGATTACTTAATTCTTCATATGCAAGCCAAAACAACGTCCGAAG CTTTT SEQ ID NO 31 10000 00 1 I MTVTYAHEPFTDFTEAKNKTAFGESLAFVNTQLGKHYPLVINGEKIETDRKIISINPANK EEIIGYASTADQELAEKAMQAALQAFDSWKKQRPEHRANILFKAAAILRRRKHEFSSYLV KEAGKPWKEADADTAEAIDFLEFYARQMLKLKEGAPVKSRAGEVNQYHYEALGVGIVISP FNFPLAIMAGTAVAAIVTGNTILLKPADAAPVVAAKFVEVMEEAGLPNGVLNYIPGDGAEIG DFLVEHPKTRFVSFTGSRAVGCRIYERAAKVQPGOKWLKRVIAEMGGKDTVLVDKDADL DLAASSIVYSAFGYSGQKCSAGSRAVIHQDVYOEVVEKAVALTKTLTVGNPEDPDTYMG PVIHEASYNKVMKYIEIGKSEGKLLAGGEGDDSKGYFIQPTIFADVDENARLMQEEIFGPV VAICKARDFDHMLEIANNTEYGLTGALLTKNRAHIERAREDFHVGNLYFNRGCTGAIVGY QPFGGFNMSGTDSKAGGPDYLILHMQAKTTSEAF SEQ ID NO 32
77. ACTGCTAGACAGAGAAATAGTCGGCAGC TCTCCGGAACGGTTAATACACGTTCAAGACGGGCACTTAGAAATCCATCCGATTGCC GGTACGAGAAAACGCGGTGCAGACAAAGCTGAAGATGAGAGACTGAAGGTTGAGCT CATGAAGGATGAAAAAGAAAAAGCGGAGCATTACATGCTCGTTGATCTTGCCCGAAA CGATATCGGCAGAGTAGCAGAGTATGGTTCTGTTTCTGTGCCGGAGTTCACAAAAAT TGTTTCCTTTTCACATGTCATGCACATTATCTCGGTGGTTACAGGCCGATTGAAAAAA GGGGTTCATCCTGTCGATGCACTGATGTCTGCTTTCCCGGCGGGGACTTTAACAGGC GCACCCAAAATCCGTGCCATGCAGCTTTTGCAAGAACTCGAGCCAACACCGAGAGAG ACATACGGAGGGTGTATTGCCTACATTGGGTTTGACGGGAATATCGACTCTTGTATTA CGATTCGCACGATGAGTGTAAAGAACGGTGTTGCATCGATACAGGCAGGTGCTGGC ATTGTTGCTGATTCTGTTCCGGAAGCCGAATACGAAGAAAGCTGTAATAAAGCCGGT _ GCGCTGCTGAAAACGATTCATATTGCAGAAGACATGTTTCATAGCAAGGAGGATAAA GCTGATGAACAGATTTCTACAATTGTGCGTTGACGGAAAAACCCTTACTGCCGGTGA GGCTGAAACGCTGATGAATATGATGATGGCAGCGGAAATGACTCCTTCTGAAATGGG GGGGATATTGTCAATTCTTGCTCATCGGGGGGAGACGCCAGAAGAGCTTGCGGGTT TIGTGAAGGCAATGCGGGCACACGCTCTTACAGTCGATGGACTTCCTGATATTGTTG ATACATGCGGAACAGGGGGAGACGGTATTTCCACTTTTAATATCTCAACGGCCTCGG CAATTGTTGCCTCGGCAGCTGGTGCGAAAATCGCTAAGCATGGCAATCGCTCTGTCT CTTCTAAAAGCGGAAGCGCTGATGTTTTAGAGGAGCTAGAGGTTTCTATTCAAACCAC TCCCGAAAAGGTCAAAAGCAGCATTGAAACAAACAACATGGGATTTCTTTTTGCGCCG CTTTACCATTCGTCTATGAAACATGTAGCAGGTACTAGAAAAGAGCTAGGTTTCAGAA CGGTATTTAATCTGCTTGGGCCGCTCAGCAATCCTTTACAGGCGAAGCGTCAGGTGA TTGGGGTCTATTCTGTTGAAAAAGCTGGACTGATGGCAAGCGCACTGGAGACGTTTC AGCCGAAGCACGTTATGTTTGTATCAAGCCGTGACGGTTTAGATGAGCTTTCAATTAC AGCACCGACCGACGTGATTGAATTAAAGGACGGAGAGCGCCGGGAGTATACCGTTT CACCCGAAGATTTCGGTTTCACAAATGGCAGACTTGAAGATTTACAGGTG
78. AGCTGCTGAAAACCTATGCTGATAAAATGAACTTAACGG CTTCTCTTTGCCACTATTCGACACAGGCTGATAAAGACCGGTTAACCGAGCATATGGAT GATCCG GCAGATGTACAAACACGGCTCGATCGAAAGGATGTTTATTACGACCAATACG GAAAAGTGGTTCTCATCCCTTTTACCATCGAGACACAGAACTATGTCATCAAGCTGACG TCTGACAGCATTGTCACGGAATTTGATTATTTGCTATTTACGTCATTAACGAGCATATAT GATTTGGTGCTGCCAATTGAGGAGGAAGGTGAAGGA SEQ ID NO 11 HHHHHH HHHHHHHHHHHHHHHHHH MVLFFQIMVWCIVAGLGLYVYATWRFEAKVKEKMSAIRKTWYLLFVLGAMVYWTYEPTSL FTHWERYLIVAVSFALIDAFIFLSAYVKKLAGSELETDTREILEENNEMLHMYLNRLKTYQY LLKNEPIHVYYGSIDAYAEGIDKLLKTYADKMNLTASLCHYSTQADKDRLTEHMDDPADV QTRLDRKDVYYDQYGKVVLIPFTIETQNYVIKLTSDSIVTEFDYLLFTSLTSIYDLVLPIEEEG EG SEQ ID NO 12 p Dit Yurin DI DI DI 1000 DI DI DI HHHHH 00000 8 DI CJ HAN EE BA ATGAAAATCAGTATGCAAAAAGCAGATTTTTGGAAAAAAGCAGCGATCTCATTACTTGTT TTCACCATGTTTTTTACCCTGATGATGAGCGAAACGGTTTTTGCGGCGGGACTGAATAA AGATCAAAAGCGCCGGGCGGAACAGCTGACAAGTATCTTTGAAAACGGCACAACGGA GATCCAATATGGATATGTAGAGCGATTGGATGACGGGCGAGGCTATACATGCGGACGG GCAGGCTTTACAACGGCTACCGGGGATGCATTGGAAGTAGTGGAAGTATACACAAAGG CAGTTCCGAATAACAAACTGAAAAAGTATCTGCCTGAATTGCGCCGTCTGGCCAAGGA AGAAAGCGATGATACAAGCAATCTCAAGGGATTCGCTTCTGCCTGGAAGTCGCTTGCA AATGATAAGGAATTTCGCGCCGCTCAAGACAAAGTAAATGACCA
79. AGGCCTCTTG TATCATTTGAAAAACACGTCAAACGGATTTCTGAACAGGATTGGGATGACCCAGTAAA AGTGGACCGGAAAGATGAAATCGGCAAATTGGGCCATACCATCGAAGAGATGCGCC AAAAGCTTGTGCAAAAGGATGAAACAGAAAGAACTCTATTGCAAAATATCTCTCATGA TTTAAAAACGCCGGTCATGGTCATCAGAGGCTATACACAATCAATTAAAGACGGGATT TTTCCTAAAGGAGACCTTGAAAACACTGTAGATGTTATTGAATGCGAAGCTCTTAAGC TGGAGAAAAAAATAAAGGATTTATTATATTTAACGAAGCTGGATTATTTAGCGAAGCAA AAAGTGCAGCACGACATGTTCAGTATTGTGGAAGTGACAGAAGAAGTCATCGAACGA TTGAAGTGGGCGCGGAAAGAACTATCGTGGGAAATTGATGTAGAAGAGGATATTTTG ATGCCGGGCGATCCGGAGCAATGGAACAAACTCCTCGAAAACATTTTGGAAAATCAA ATCCGCTATGCTGAGACAAAAATAGAAATCAGCATGAAACAAGATGATCGAAATATCG TGATCACCATTAAAAATGACGGTCCGCATATTGAAGATGAGATGCTCTCCAGCCTCTA TGAGCCTTTTAATAAAGGGAAGAAAGGCGAATTCGGCATTGGTCTAAGCATCGTAAAA CGAATTTTAACTCTTCATAAGGCATCTATCTCAATTGAAAATGACAAAACGGGTGTATC ATACCGCATAGCAGTGCCAAAA SEQ ID NO 17 DI L1 DI 0 IU o O o O n o O O MKNKPLAFQI WVVISGILLAISILLLVLFSNTLRDFFTNETYTTIENEQHVLTEYRLPGSIE RRYYSEEATAPTTVRSVQ HVLLPENEEASSDKDLSILS SSFIHKVYKLADKQEAKKKR YSADVNGEKVFFVIKKGLSVNGQSAMMLSYALDSYRDDLAYTLFKQLLFIIAVVILLSWIPAI WLAKYLSRPLVSFEKHVKRISEODWDDPVKVDRKDEIGKLGHTIEEMROKLVOKDETER TLLONISHDLKTPVMVIRGYTOSIKDGIFPKGDLENTVDVIECEALKLEKKIKDLLYLTKLDY LAKQKVQHDMFSIVEVTEEVIERLKWARKELSWEIVEEDILMPGDPEQWNKLLENILENQI RYAETKIEISMKQDDRNIVITIKNDGPHIEDEMLSSLYEPFNKGKKGEFGIGLSIVKRILTLHK ASISIENDKTGVSYRIA
80. AT 81 Bomb PKSUF Xtal GAGCCTCTAGAGCCCATIGAATCATTTGTTT 718 PKS DF 801 GAGCCGGRTCCATITCGGGGTTCTCAAAAARA 86 SF Xbal GAAGTTGTAGAGATTGTAATTACAAAAGGGGGGTG 88 Skin UR BamHi GAAGTGGATCCTTTCACOGATCATAAAAGCOG fo Skin DF BamHI TGAAAGGATCCATTTTTCATTGATTGTTAAGTC GCTTATGGATCCGATACAAGAGAGGTCTCTCG Spec UF BamHl ACTGATGGATCCATOGATITTCGTTCGTGAATACATG Ja Spec DR BamHl ACTGATGGATCCCATATGCAAGGGTITATTGTTTTG 95 CssSUF Xbal GCACGTTCTAGACCACOGTCOCCTGTGTTGTATGCAC JA CssS DF BamHl TGACAAGGATCCTGTATCATACOGCATAGCAGTGCC 98 CssSLDR Sad TTOCGCGAGCTOGGCGAGAGCTTCAGACTCCGTCAGA 99 Baril PhrC UE PhrCF POUR Ps GCTTATAAGCTTCTGTCATGGCGCATYAACG 106 BEDR 107 CGTGAA AAGCTT TCGCGGGATGTATGAATTTGATAAG 108 GTAGGGAGCTC GATGCGCCACAATGTCGGTACAACG 109 REDE Xbal tk TCTAGA BamHI GGATCC SacI GAGCTC Asp718 GGTACC PstI CTGCAG HindIII AAGCTT Pphage 000 HB EEE B ED
81. ATCACGCTGAACGGAAAAACATATCAACTGGAAAACACCT GCTTTGCGACGATTAATCCGGAGCAGCCAGATCAGCTATTAGAAGAAGAAGCAGAAG TCATAGACAAGCTGCTATTCTCTGTCCAGCATTCCGAAAAGCTGGGCCGCCATATGA ATTTTATGATGAAAAAAGGCAGCCTTTATTTAAAATATAACGGCAACCTGTTGATTCAC GGCTGTATTCCAGTTGATGAAAACGGCAATATGGAAACGATGATGATTGAGGATAAA CCGTATGCGGGCCGTGAGCTGCTCGATGTATTTGAACGATTCTTGCGGGAAGCCTTT GCCCACCCGGAAGAAACCGATGACCTGGCGACAGATATGGCTTGGTAT TTATGGACA GGCGAATACTCCTCCCTCTTCGGAAAACGCGCCATGACGACATTTGAGCGCTATTTC ATCAAAGAGAAGGAAACGCATAAAGAGAAGAAAAACCCGTATTATTATTTACGAGAAG ACGAGGCAACCTGCCGAAACATCCTGGCAGAATTCGGCCTCAATCCAGATCACGGC CATATCATCAACGGCCATACACCTGTAAAAGAAATCGAAGGAGAAGACCCAATCAAA GCAAACGGAAAAATGATCGTCATCGACGGCGGCTTCTCCAAAGCCTACCAATCCACA ACAGGCATCGCCGGCTACACGCTGCTATACAACTCCTACGGCATGCAGCTCGTCGC CCATAAACACTTCAATTCCAAGGCAGAAGTCCTAAGCACCGGAACCGACGTCTTAAC GGTCAAACGATTAGTGGACAAAGAGCTTGAGCGGAAGAAAGTGAAGGAAACGAATGT GGGTGAGGAATTGTTGCAGGAAGTTGCGATTTTAGAGAGTTTGCGGGAGTATCGGTA TATGAAG SEQ ID NO 19 CJ CJ CJ E UO UI DU 40 20 30 O 47 JP 2007 532114 A 2007 11 15 o O MFKNNVILLNSPYHAHAHKEGFILKRGWTVLESKYLDLLAQKYDCEEKVVTEIINLKAILNL PKGTEHFVSDLHGEYQAFQHVLRNGSGRVKEKIRDIFSGVIYDREIDELAALVYYPED KLKLIKHDFDAKEALNEWYKETIHRMIKLVSYCSSKYTRSKLRKALPAQFAYITEELLYK TEQAGNKEQYYSEIIDQIIELGQADKLITGLAYSVQRLVVDHLHVVGDIYDRGPQPDRIM EELINYHSVDIQWGNHDVLWIGAYSGSKVCLANIIRICARYDNLDIIEDVYGINLRPLLN LAEKYYDDNPAFRPKADENRPEDEIKQITKIHQAIAMIQFKLESPIIKRRPNFNMEERLL LEKI
82. ATCAGT GAGAACGATTGCGGGTACATTTACAATGCATCAAGAGCTTGAGAAAAAGCTGGCAGC CTTTAAAAAAACGGAGGCGGCACTTGTATTCCAATCAGGCTTCACAACAAACCAAGG CGTACTTTCAAGTATTCTATCAAAAGAGGACATTGTCATCTCAGATGAATTGAACCAT GCCTCTATTATTGACGGAATTCGACTGACAAAGGCGGATAAAAAGGTGTATCAGCAC GTCAATATGAGTGATTTAGAGCGGGTGCTGAGAAAGTCAATGAATTATCGGATGCGT CTGATTGTGACAGACGGCGTATTTTCCATGGATGGCAACATAGCTCCTCTGCCTGATA TTGTAGAGCTCGCTGAGAAATATGACGCATTTGTGATGGTGGATGACGCCCATGCAT CCGGAGTACTTGGCGAAAACGGCAGGGGAACGGTGAATCACTTCGGTCTTGACGGC AGAGTGCATATTCAGGTCGGAACATTAAGCAAGGCAATCGGAGTGCTCGGCGGCTA CGCTGCAGGTTCAAAGGTGCTGATCGATTATTTGCGCCATAAAGGCCGTCCATTTTTA TTCAGCACATCTCATCCGCCGGCAGTCACTGCAGCTTGTATGGAAGCGATTGATGTC TTGCTTGAAGAGCCGGAGCATATGGAGCGCTTGTGGGAGAATACTGCCTATTTTAAA GCAATGCTTGTGAAAATGGGTCTGACTCTCACGAAGAGTGAAACGCCGATTCTTCCT ATTTTAATAGGTGATGAAGGTGTGGCAAAGCAATTTTCAGATCAGCTCCTTTCTCGCG GTGTTTTTGCCCAAAGTATCGTTTTCCCGACTGTAGCAAAGGGAAAAGCCAGAATTCG CACGATTATAACAGCAGAGCACACCAAAGATGAACTGGATCAGGCGCTTGATGTCAT CGAAAAGACGGCAAAGGAGCTCCAGCTATTG SEQ ID NO 25 20 10 MIKEFEFLKAELNSMKENHTWQDIKQLESMQGPSVTVNHQKVIQLSSNNYLGFTSHPRLI NAAQEAVQQYGAGTGSVRTIAGTFT MHQELEKKLAAFKKTEAALVFQSGFTTNQGVLSSI LSKEDIVISDELNHASIIDGIRLTKADKKVYQHVNMSDLERVLRKSMNYRMRLIVTDGVFS MDGNIAPLPDIVELAEKYDAFVMVDDAHASGVLGENGRGTVNHFGLDGRVHIQVGTLSK AIGVLGGYAAGSKVLIDYLRHKGRPFLFSTSHPPAVTAACMEAIDVLLEEPEHMERLWEN TAYFKAMLVKMGLTLTKSETPILPILIGDEGVAKQFSDQLLSRGVFAQSIVFPT
83. ATGTCCTTTCAGACCGTGAGAAACAAA TCATAGACCTTACGTATATTCAAAACAAAAGCCAAAAAGAAACTGGGGACATTCTCGGT ATATCTCAAATGCACGTCTCGCGCTTGCAACGCAAAGCTGTGAAGAAGCTCAGAGAGG CCTTGATTGAAGATCCCTCGATGGAGTTAATG SEO ID NO 9 n 0000000000000 DU MIMTQPSKTTKLTKDEVDRLISDYQTKQDEQAQETLVRVYTNLVDMLAKKYSKGKSFHED LRQVGMIGLLGAIKRYDPVVGKSFEAFAIPTIIGEIKRFLRDKTWSVHVPRRIKELGPRIKMA VDQLTTETQRSPKVEEIAEFLDVSEEEVLETMEMGKSYQALSVDHSIEADSDGSTVTILDI VGSQEDGYERVNQQLMLQSVLHVLSDREKQIIDLTYIQNKSQKETGDILGISQMHVSRLQ RKAVKKLREALIEDPSMELM SEQ ID NO 10 mmm DI E 8 10 20 30 43 JP 2007 532114 A 2007 11 15 ATGGTTTTATTCTTTCAGATCATGGTCTGGTGCATCGTGGCCGGACTGGGGTTATACGT GTATGCCACGTGGCGTTTCGAAGCGAAGGTCAAAGAAAAAATGTCCGCCATTCGGAAA ACTTGGTATTTGCTGTTTGTTCTGGGCGCTATGGTATACTGGACATATGAGCCCACTTC CCTATTTACCCACTGGGAACGGTATCTCATTGTCGCAGTCAGTTTTGCTTTGATTGATG CTTTTATCTTCTTAAGTGCATATGTCAAAAAACTGGCCGGCAGCGAGCTTGAAACAGAC ACAAGAGAAATTCTTGAAGAAAACAACGAAATGCTCCACATGTATCTCAATCGGCTGAA AACATACCAATACCTATTGAAAAACGAACCGATCCATGTTTATTATGGAAGTATAGATGC TTATGCTGAAGGTATTGATA
84. CAAGCTGGGCTGTGTGCACG AACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCG GTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTA TGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGT ATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATC CGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTITGTT TGCAAGCAGCAGATTACGCGCAG AAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGA AAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAA ATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAA TGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGAC TCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATG ATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAG GGCCGAGCGCAGAAGTGGTCCTGCAACTITATCCGCCTCCATCCAGTCTATTAATTGTTGCCG GGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGG CATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAG GCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGT TGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTT ACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAG AATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAACACGGGATAATACCGCGCCA CATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGG ATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCAT CTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGG GAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATT TATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAAT
85. CAGAGGAGGTGA 137 pa 137 Sir Uffus BamHI GCCAATAAGTTCTCTITAGAGAACAGGATCC 138 GCTTACCGAAAGCCAGACTCAGCAA SIr Urfus BamHI TTGCTGAGTCTGGCTTTCGGTAAGCGGATCCTTGTICTCT 139 AAAGAGAACTTATTGGC Sir Dffus BamHI CGTTAATGCGCCATGACAGCCATGAGGATCG 140 GGGCTAACGTTCGCATCTATAGGGG Slr Drfus BamHI CCCCTATAGATGCGAACGTTAGCCC GGATCC 141 TCATGGCTGTCATGGCGCATTAACG Sir DR TGAGACGAGCTCGATGCATAGGCGACGGCAGGGCGCC 142 Sir UF nested CGAAATTCTAGATCCCGCGATTCCGCCCTTTGTGG 143 Slr DR nested TTCCAAGAGCTCGCGGAATACCGGAAGCAGCCCC 144 YbcO U CAATTCTCTAGAGCGGTCGGCGCAGGTATAGGAGGGG 14 F 5 YbcO UF BamHI GAAAAGAAACCAAAAAGAATGGGAAGGATCC 146 GCTTACCGAAAGCCAGACTCAGCAA YbcO UR BamHi TTGCTGAGTCTGGCTTTCGGTAAGCGGATCC 147 TTCCCATTCTTTTTGGTTTCTTTTC YbcO DF BamHI CGTTAATGCGCCATGACAGCCATGAGGATCC 148 GCTATTTAACATTTGAGAATAGGGA 20 YbcO DR BamHl TCCCTATTCTCAAATGTTAAATAGCGGATCC 149 TCATGGCTGTCATGGCGCATTAACG 30 YbcO DR Sac CAGGCGGAGCTCCCATTTATGACGTGCTTCCCTAAGC Csn UF TACGAATCTAGAGATCATTGCGGAAGTAGAAGTGGAA ENIK RR 83 JP 2007 532114 A 2007 11 15 4 Csn UF BamHI TITAGATTGAGTTCATCTGCAGCGGGGATCC 152 GCTTACCGAAAGCCAGACTCAGCAA Csn UR BamHI TTGCTGAGTCTGGCTITCGGTAAGCGGATCC 153 CCGCTGCAGATGAACTCAATCTAAA Csn DF BamHl CGTTAATGCGCCATGACAGCCATGAGGATCC 154 GCCAATCAGCCTTAGCCCCTCTCAC Csn DR BamHI GTGAGAGGGGCTAAGGCTGATTGGCGGATCC 155 TCATGGCTGTCATGGCGCATTAACG ATACTCGTCGACATACGTTGAATTGCCGAGAAGCCGC
86. CAGTCTCC GAAAGAGAGCGCTTATCTCATTCAGAATATTTTTGAAAATAAAAGCAGCAGTTCCGCT TTATCTATTACGGCTTTTAATGCGGGTGCTGCGATTTACACGGCGGGAATTACCGCCT CACTGAAGGAAGGAACGGAGCTGGCGTTAGAGACGATTACAAGCGGAGGCGCTGCC GCGCAGCTTGAACGACTAAAGCAGAAAGAGGAAGAGATCTATGCTTGAAAAAATCAT CAAACAAAAGAAAGAAGAAGTGAAAACACTGGTTCTGCCGGTAGAGCAGCCTTTCGA GAAACGTTCATTTAAGGAGGCGCCGGCAAGCCCGAATCGGTTTATCGGGTTGATTGC CGAAGTGAAGAAAGCATCGCCGTCAAAAGGGCTTATTAAAGAGGATTTTGTACCTGT GCAGATTGCAAAAGACTATGAGGCTGCGAAGGCAGATGCGATTTCCGTTTTAACAGA CACCCCGTTTTTITCAAGGGGAAAACAGCTATTTATCAGACGTAAAGCGTGCTGTTTCG ATTCCTGTACTTAGAAAAGATTTTATTATTGATTCTCTTCAAGTAGAGGAATCAAGAAG 000000 10 20 30 50 57 JP 2007 532114 A 2007 11 15 10000 AATCGGAGCGGATGCCATATTGTTAATCGGCGAG GTGCTTGATCCCTTACACCTTCAT GAATTATATCTTGAAGCAGGTGAAAAGGGGATGGACGTGTTAGTGGAGGTTCATGAT GCATCAACGCTAGAACAAATATTGAAAGTGTTCACACCCGACATTCTCGGCGTAAATA ATCGAAACCTAAAAACGTTTGAAACATCTGTAAAGCAGACAGAACAAATCGCATCTCT CGTTCCGAAAGAATCCTTGCTTGTCAGCGAAAGCG GAATCGGTTCTTTAGAACATTTA ACATTTGTCAATGAACATGGGGCGCGAGCTGTACTTATCGGTGAATCATTGATGAGA CAAACTICTCAGCGTAAAGCAATCCATGCTTTGTTTAGGGAGTGAG GTTGTGAAGAAA CCGGCATTAAAATATTGCGGTATTCGGTCACTAAAGGATTTGCAGCTTGCGGCGGAA TCACAGGCTGATTACCTAGGATTTATTTTTG CTGAAAGCAAACGAAAAGTATCTCCGG AAGATGTGAAAAAATGGCTGAACCAAGTTCGTGTCGAAAAACAGGTTGCAGGTGTTTT TGTTAATGAATCAATAGAGACGATGTCACGTATTGCCAAGAGCTTGAAGCTCGACGTC ATTCAGCTTCACGGTGATGAAAAACCGGCGGATGTCGCTGCTCTTCGCAAGCTGACA GGCTGTGAAATATGGAAGGCGCTTCACCATCAAGATAACACAACTCAAGAAATAGCC CGCTTTA
87. CCTGTTCCGAACGTCTCATTGGTTGATCTCGTTGTTGATCTG AAAACGGATGTTACGGCTGAAGAAGTAAACGAGGCATTTAAACGCGCTGCCAAAACG TCGATGTACGGTGTACTTGATTACTCAGATGAACCGCTCGTTTCGACTGATTATAATA CGAATCCGCATTCAGCGGTCATTGACGGGCTTACAACAATGGTAATGGAAGACAGGA AAGTAAAGGTGCTGGCGTGGTATGACAACGAATGGGGCTACTCCTGCAGAGTTGTTG ATCTAATCCGCCATGTAGCGGCACGAATGAAACATCCGTCTGCTGTA SEQ ID NO 23 20 10000 MKVKVAINGFGRIGRMVFRKAMLDDQIQVVAINASYSAETLAHLIKYDTIHGRYDKEVVA GEDSLIVNGKKVLLLNSRDPKQLPWREYDIDIVVEATGKFNAKDKAMGHIEAGAKKVILT APGKNEDVTIVMGVNEDQFDAERHVIISNASCTTNCLAPVVKVLDEEFGIESGLMTTVHAY TNDQKNIDNPHKDLRRARACGESIIPTTTGAAKALSLVLPHLKGKLHGLALRVPVPNVSLV DLVVDLKTDVTAEEVNEAFKRAAKTSMYGVLDYSDEPLVSTDYNTNPHSAVIDGLTTMVM EDRKVKVLAWYDNEWGYSCRVVDLIRHVAARMKHPSAV SEQ ID NO 24 30 o o o n 49 JP 2007 532114 A 2007 11 15 LE DL H D ATGACGAAGGAATTTGAGTTTTTAAAAGCAGAGCTTAATAGTATGAAAGAAAACCATA CATGGCAAGACATAAAACAGCTTGAATCTATGCAGGGCCCATCTGTCACAGTGAATC ACCAAAAAGTCATTCAGCTATCTTCTAATAATTACCTCGGATTCACTTCACATCCTAGA CTCATCAACGCCGCACAGGAGGCCGTTCAGCAGTATGGAGCCGGCACCGG
88. CGA 20 AACGCA SEQ ID NO 33 MTALSKSKEIIDQTSHYGANNYHPLPIVISEALGAWVKDPEGNEYMDMLSAYSAVNQGHR HPKIIQALKDQADKITLTSRAFHNDQLGPF YEKTAKLTGKEMILPMNTGAEAVESAVKAAR RWAYEVKGVADNQAEIIACVGNFHGRTMLAVSLSSEEEYKRGFGPMLPGIKLIPYGDVEA LRQAITPNTAAFLFEPIQGEAGIVIPPEGFLQEAAAICKEENVLFIADEIQTGLGRTGK TFACDWDGIVPDMYILGKALGGGVFPISCIAADREILGVENPGSHGSTFGGNPLACAVSI 30 ASLEVLEDEKLADRSLELGEYFKSELESIDSPVIKEVRGRGLFIGVELTEAARPY CERLK EEGLLCKETHDTVIRFAPPLIISKEDLDWAIEKIKHVLRNA SEQ ID NO 34 54 JP 2007 532114 A 2007 11 15 ATGGATAAAACGATTTCGGTTATTGGAATGCCAATGGATTTAGGACAAGCACGACGC GGAGTGGATATGGGCCCGAGTGCCATCCGGTACGOTCATCTGATCGAGAGGCTGTC AGACATGGGGTATACGGTTGAAGATCTCGGTGACATTCCGATCAATCGCGAAAAAAT CAAAAATGACGAGGAACTGAAAAACCTGAATTCCGTTTTGGCGGGAAATGAAAAACT CGCGCAAAAGGTCAACAAAGTCATTGAAGAGAAAAAATTCCCGCTTGTCCTGGGCGG TGACCACAGTATTGCGATCGGCACGCTTGCAGGCACAGCGAAGCATTACGATAATCT CGGCGTCATCTGGTATGACGCGCACGGCGATTTGAATACACTTGAAACTTCACCATC GGGCAATATTCACGGCATGCCGCTCGCGGTCAGCCTAGGCATTGGCCACGAGTCAC TGGTTAACCTTGAAGGCTACGCGCCTAAAATCAAACCGGAAAACGTCGTCATCATTG
89. CTCTGCTAAAATTCCTGAAAAATTTTGCAAAAAGTTGTTGACTTTATCTACAAG GTGTGGCATAATGTGTGGAATTGTGAGCGGATAACAATTAAGCTTAGGAGGGAGTGTTAAATG TCCAATTTACTGACCGTACACCAAAATTTGCCTGCATTACCGGTCGATGCAACGAGTGATGAG GTTCGCAAGAACCTGATGGACATGTTCAGGGATCGCCAGGCGTTTTCTGAGCATACCTGGAAA ATGCTTCTGTCCGTTTGCCGGTCGTGGGCGGCATGGTGCAAGTTGAATAACCGGAAATGGTTT CCCGCAGAACCTGAAGATGTTCGCGATTATCTTCTATATCTTCAGGCGCGCGGTCTGGCAGTA AAAACTATCCAGCAACATTTGGGCCAGCTAAACATGCTTCATCGTCGGTCCGGGCTGCCACGA CCAAGTGACAGCAATGCTGTTTCACTGGTTATGCGGCGGATCCGAAAAGAAAACGTTGATGCC GGTGAACGTGCAAAACAGGCTCTAGCGTTCGAACGCACTGATTTCGACCAGGTTCGTTCACTC ATGGAAAATAGCGATCGCTGCCAGGATATACGTAATCTGGCATTTCTGGGGATTGCTTATAACA CCCTGTTACGTATAGCCGAAATTGCCAGGATCAGGGTTAAAGATATCTCACGTACTGACGGTG GGAGAATGTTAATCCATATTGGCAGAACGAAAACGCTGGTTAGCACCGCAGGTGTAGAGAAG GCACTTAGCCTGGGGGTAACTAAACTGGTCGAGCGATGGATTTCCGTCTCTGGTGTAGCTGAT GATCCGAATAACTACCTGTTTTGCCGGGTCAGAAAAAATGGTGTTGCCGCGCCATCTGCCACC AGCCAGCTATCAACTCGCGCCCTGGAAGGGATTTTTGAAGCAACTCATCGATTGATTTACGGC GCTAAGGATGACTCTGGTCAGAGATACCTGGCCTGGTCTGGACACAGTGCCCGTGTCGGAGC 10 20 30 88 JP 2007 532114 A 2007 11 15 00000 CGCGCGAGATATGGCCCGCGCTGGAGTTTCAATACCGGAGATCATG CAAGCTGGTGGCTGGA CCAATGTAAATATTGTCATGAACTATATCCGTAACCTG GATAGTGAAACAGGGGCAATGGTGC GCCTGCTGGAAGATGGCGATTAGGAGCTCGCATCACACGCAAAAAGGAAATTGGAATAAATGC GAAATTTGAGATGTTAATTAAAGACCTTTTTGAGGTCTTTTTTTCTTAGATTTTTGGGGTTATTTA GGGGAGAAAACATAGGGGGGTACTACGACCTCCCCCCTAGGTGTCCATTGTCCATTGTCCAA ACAAATAAATAAATATTGGGTTTTTAATGTTAAAAG GTTGTTT
90. D 10 D HHHHHHHHHHHH 50 JP 2007 532114 A 2007 11 15 67 D D 10 D 20 30
91. DYDKNEITLNGKTYQLENTCFATINPEQPDQLLEEEAEVIDKLLFSVQHSEKLGRH MNFMMKKGSLYLKYNGNLLIHGCIPVDENGNMETMMIEDKPYAGRELLDVFERFLREAF AHPEETDDLATDMAWYLWTGEY SSLFGKRAMTTFERYFIKEKETHKEKKNPYYYLREDE ATCRNILAEFGLNPDHGHIINGHTPVKEIEGEDPIKANGKMIVIDGGFSKAYQSTTGIAGYT LLYNSYGMQLVAHKHFNSKAEVLSTGTDVLTVKRLVDKELERKKVKETNVGEELLQEVAI LESLREYRYMK SEQ ID NO 20 HHHH ATGAAACGAGAAAGCAACATTCAAGTG CTCAGCCGTGGTCAAAAAGATCAGCCTGTG AGCCAGATTTATCAAGTATCAACAATGACTTCTCTATTAGACGGAGTATATGACGGAG ATTTTGAACTGTCAGAGATTCCGAAATATGGAGACTTCGGTATCGGAACCTTTAACAA GCTTGACGGAGAGCTGATTGGGTTTGACG GCGAATTTTACCGTCTTCGCTCAGACGG AACCGCGACACCG GTCCAAAATGGAGACCGTTCACCGTTCTGTTCATTTACGTTCTTT ACACCGGACATGACG CACAAAATTGATGCGAAAATGACACGCGAAGACTTTGAAAAA GAGATCAACAGCATG CTGCCAAGCAGAAACTTATTTTATGCAATTCGCATTGACGGAT TGTTTAAAAAG GTGCAGACAAGAACAGTAGAACTTCAAGAAAAACCTTACGTGCCAAT GGTTGAAGCG GTCAAAACACAGCCGATTTTCAACTTCGACAACGTGAGAGGAACGAT TGTAGGTTTCTTGACACCAGCTTATGCAAACGGAATCG CCGTTTCTGGCTATCACCTG CACTTCATTGACGAAGGACGCAATTCAGGCGGACACGTTTTTGACTATGTGCTTGAG GATTG CACGGTTACGATTTCTCAAAAAATGAACATGAATCTCAGACTTCCGAACACAG CGGATTTCTTTAATG CGAATCTGGATAACCCTGATTTTGCGAAAGATATCGAAACAAC TGAAGGAAGCCCTGAA SEQ ID NO 21 Uti D
92. GATACACGCGAA GCCAATTATGATGATTCCTTCTATACTGAAAACACGCGGGCAGCTTACCCGATTCATA TGATTAATAACATCGTGACTCCAAGCATGGCCGGCCATCCGTCAGCCATTGTATTTTT GACGGCTGATGCCTTCGGAGTCCTGCCGCCGATCAGCAAACTAACGAAGGAGCAGG TGATGTACCATTTTTTGAGCGGTTACACGAGTAAGCTTGCCGGAACCGAACGTGGTG TCACGTCTCCTGAAACGACGTTTTCTACATGCTTCGGCTCACCGTTCCTGCCGCTTCC TGCTCACGTCTATGCTGAAATGCTCGGCAAAAAGATCGATGAACACGGCGCAGACGT TITCTTAGTCAATACCGGATGGACCGGGGGCGGCTACGGCACAGGCGAACGAATGA AGCTTTCTTACACTAGAGCAATGGTCAAAGCAGCGATTGAAGGCAAATTAGAGGATG CTGAAATGATAACTGACGATATTTTCGGCCTGCACATTCCGGCCCATGTTCCTGGCGT TCCTGATCATATCCTTCAGCCTGAAAACACGTGGACCAACAAGGAAGAATACAAAGAA AAAGCAGTCTACCTTGCAAATGAATTCAAAGAGAACTTTAAAAAGTTCGCACATACCG ATGCCATCGCCCAGGCAGGCGGCCCTCTCGTA SEQ ID NO 27 l HHHHHHHHHHHHHHHHHHH 0000 MNSVDLTADLQALLTCPNVRHNLSAAQLTEKVLSRNEGILTSTGAVRATTGAYTGRSPKD KFIVEEESTKNKIDWGPVNOPISEEAFERLYTKVVSYLKERDELFVFEGFAGADEKYRLPI TVVNEFAWHNLFARQLFIRPEGNDKKTVEQPFTILSAPHFKADPKTDGTHSETFIIVSF EKRTILIGGTEYAGEMKKSIFSIMNFLLPERDILSMHCSANVGEKGDVALFFGLSGTGKT TLSADADRKLIGDDEHGWSDTGVFNIEGGCYAKCIHLSEEKEPQIFNAIRFGSVLENVVV DEDTREANYDDSFYTENTRAAYPIHMINNIVTPSMAGHPSAIVFLTADAFGVLPPISKLT KEQVMYHFLSGYTSKLAGTERGVTSPETTFSTCFGSPFLPLPAHVYAEMLGKKIDEHGAD VFLVNTGWTGGGYGTGERMKLSYTRAMVKAAIEGKLEDAEMITDDIFGLHIPAHVPGVPD HILQPENTWTNKEEYKEKAVYLANEFKENFKKFAHTDAIAQAGGPLV SEQ ID NO 28
93. GCATCGTAGAGGGC GTGGGAGAGAATGTCAGCAGTGTAAAAGTGGGAGAGTATGTGTCTGCGGAAACACA CATTGTCTGTGGTGAATGTGTCCCTTGCCTAACAGGAAAATCTCATGTGTGTACCAAT ACTGCTATAATCGGAGTGGACACGGCAGGCTGTTTTGCGGAGTATGTAAAAGTTCCA GCTGATAACATTTGGAGAAATCCCGCTGATATGGACCCGTCGATTGCTTCCATTCAAG AGCCTTTAGGAAATGCAGTTCATACCGTACTCGAGAGCCAGCCTGCAGGAGGAACGA CTGCAGTCATTGGATGCGGACCGATTGGTCTTATGGCTGTTGCGGTTGCAAAAGCAG CAGGAGCTTCTCAGGTGATAGCGATTGATAAGAATGAATACAGGCTGAGGCTTGCAA AACAAATGGGAGCGACTTGTACTGTTTCTATTGAAAAAGAAGACCCGCTCAAAATTGT AAGCGCTTTAACGAGTGGAGAAGGAGCAGATCTTGTTTGTGAGATGTCGGGCCATCC CTCAGCGATTGCCCAAGGTCTTGCGATGGCTGCGAATGGCGGAAGATTTCATATTCT CAGCTTGCCGGAACATCCGGTGACAATTGATTTGACGAATAAAGTGGTATTTAAAGG GCTTACCATCCAAGGAATCACAGGAAGAAAAATGTTTTCAACATGGCGCCAGGTGTC TCAGTTGATCAGTTCAAACATGATCGATCTTGCACCTGTTATTACCCATCAGTTTCCAT TAGAGGAGTTTGAAAAAGGTTTCGAACTGATGAGAAGCGGGCAGTGCGGAAAAGTAA TTTTAATTCCA SEQ ID NO 37 10000000 CJ MQSGKMKALMKKDGAFGAVLTEVPIPEIDKHEVLIKVKAASICGTDVHIYNWDQWARQRI KTPYVFGHEFSGIVEGVGENVSSVKVGEYVSAETHIVCGECVPCLTGKSHVCTNTAIIGV DTAGCFAEYVKVPADNIWRNPADMDPSIASIQEPLGNAVHTVLESQPAGGTTAVIGCGPI GLMAVAVAKAAGASQVIAIDKNEYRLRLAKQMGATCTVSIEKEDPLKIVSALTSGEGADLV CEMSGHPSAIAQGLAMAANGGRFHILSLPEHPVTIDLTNKVVFKGLTIQGITGRKMFSTW RQVSQLISSNMIDLAPVITHQFPLEEFEKGFELMRSGQCGKVILIP SEQ ID NO 38
94. GCGGCGGGCCATTACCAGGCCGAAGCAGCGTTGTTGCAGT GCACGGCAGATACACTTGCTGATGCGGTGCTGATTACGACCGCTCACGCGTGGCAGCATCAG GGGAAAACCTTATTTATCAGCCGGAAAA CCTACCGGATTGATGGTAGTGGTCAAATGGCGATT ACCGTTGATGTTGAAGTGGCGAGCGATACACCGCATCCGGCGCGGATTGGCCTGAACTGCCA GCTGGCGCAGGTAGCAGAGCGGGTAAACTGGCTCG GATTAGGGCCGCAAGAAAACTATCCC GACCGCCTTACTGCCGCCTGTTTTGACCGCTGGGATCTGCCATTGTCAGACATGTATACCCCG TACGTCTTCCCGAGCGAAAACGGTCTGCGCTGCGGGACGCGCGAATTGAATTATGGCCCACA CCAGTGGCGCGGCGACTTCCAGTTCAACATCAGCCGCTACAGTCAACAGCAACTGATGGAAA CCAGCCATCGCCATCTGCTGCACG CGGAAGAAGGCACATGGCTGAATATCGACGGTTTCCAT ATGGGGATTGGTGGCGACGACTCCTGGAGCCCGTCAGTATCGGCGGAATTCCAGCTGAGCG CCGGTCGCTACCATTACCAGTTGGTCTGGTGTCAAAAATAATAATAACCG GGCAGGCCATGTC TGCCCGTATTTCG CGTAAGGAAATCCATTATGTACTATTTCAAGCTAATTCCGGTGGAAACGAG GTCATCATTTCCTTCCGAAAAAACGGTTGCATTTAAATCTTACATATGTAATACTTTCAAAGACT ACATTTGTAAGATTTGATGTTTGAGTCGGCTGAAAGATCGTACGTACCAATTATTGTTTCGTGAT TGTTCAAGCCATAACACTGTAGG GATAGTGGAAAGAGTGCTTCATCTGGTTACGATCAATCAAA TATTCAAACGGAGGGAGACGATTTTGATGAAACCAGTAACGTTATACGATGTCGCAGAGTATG CCGGTGTCTCTTATCAGACCGTTTCCCGCGTGGTGAACCAGGCCAGCCACGTTTCTGCGAAAA CGCGGGAAAAAGTGGAAGCGGCGATGGCGGAGCTGAATTACATTCCCAACCGCGTGGCACAA CAACTGGCGGGCAAACAGTCGTTG CTGATTGGCGTTGCCACCTCCAGTCTGGCCCTGCACGC GCCGTCGCAAATTGTCGCGGCGATTAAATCTCGCGCCGATCAACTGGGTGCCAGCGTGGTGG TGTCGATGGTAGAACGAAGCGG CGTCGAAGCCTGTAAAGCGGCGGTGCACAATCTTCTCGCG CAACGCGTCAGTGGGCTGATCATTAACTATCCG CTGGATGACCAGGATGCCATTGCTGTGGAA GCTGCCTGCACTAATGTTCCGGCGTTATTTCTTGATGTCTCTGACCAGACACCCATCAACAGTA TTATTTTCTCCCA
95. GCTAAACCTGACAGTGCAGATGTTTATATGGGACCTGTCA TTGACCAAGGTTCTTATGATAAAATTATGAGCTATATTGAGATCGGAAAACAGGAAGG GCGTTTAGTAAGCGGCGGTACTGGTGATGATTCGAAAGGATACTTCATCAAACCGAC GATCTTCGCTGACCTTGATCCGAAAGCAAGACTCATGCAGGAAGAAATTTTCGGACC TGTCGTTGCATTTTGTAAAGTGTCAGACTTTGATGAAGCTTTAGAAGTGGCAAACAAT ACTGAATATGGTTTGACAGGCGCGGTTATCACAAACAACCGCAAGCACATCGAGCGT GCGAAACAGGAATTCCATGTCGGAAACCTATACTTCAACCGCAACTGTACAGGTGCT ATCGTCGGCTACCATCCGTTTGGCGGCTTCAAAATGTCGGGAACGGATTCAAAAGCA GGCGGGCCGGATTACTTGGCTCTGCATATGCAAGCAAAAACAATCAGTGAAATGTTC SEQ ID NO 54 HHHHHHHHHHHHHHHHHHH mu 10 20 30 61 JP 2007 532114 A 2007 11 15 DU MTTPYKHEPFTNFQDQNYVEAFKKALATVSEYLGKDYPLVINGERVETEAKIVSINPADK EEVVGRVSKASQEHAEQAIQAAAKAFEEWRYTSPEERAAVLFRAAAKVRRRKHEFSALL VKEAGKPWNEADADTAEAIDFMEYYARQMIELAKGKPVNSREGEKNQYVYTPTGVTVVI PPWNFLFAIMAGTTVAPIVTGNTVVLKPASATPVIAAKFVEVLEESGLPKGVVNFVPGSGS EVGDYLVDHPKTSLITFTGSREVGTRIFERAAKVQPGQQHLKRVIAEMGGKDTVVVDEDA DIELAAQSIFTSAFGFAGQKCSAGSRAVVHEKVYDQVLERVIEITESKVTAKPDSADVYMG PVIDQGSYDKIMSYIEIGKQEGRLVSGGTGDDSKGYFIKPTIFADLDPKARLMQEEIFGPVV AFCKVSDFDEALEVANNTEYGLTGAVITNNRKHIERAKQEFHVGNLYFNRNCTGAIVGYH PFGGFKMSGTDSKAGGPDYLALHMQAKTISEMF SEQ ID NO 55 l
96. GGTTGTGCAACATG CTCGATCGGAGCCG CTTGTCTAGTGGACGGTCCTATCCCTGATTI GAAATTGCCGGTGCAACAGGTCTATTC GGTCTATGGGGG SEQ ID NO 1 HHHHH DI 00000060 AA 10 1 UU MKKAVIVENKGCATCSIGAACLVDGPIPDFEIAGATGLFGLWG SEQ ID NO 2 J E E E E A E E E O IO E E EJ 20 VUDDUUUDUUUDUUUDOU UUD ATGATTGGAAGAATTATCCGTTTGTACCGTAAAAGAAAAGGCTATTCTATTAATCAG CTG GCTGTTGAGTCAGGCGTATCCAAATCCTATTTAAG CAAGATTGAAAGAGGCGTTCACAC GAATCCGTCCGTTCAATTTTTAAAAAAAGTTTCTG CCACACTGGAAGTTGAATTAACAGA ATTATTTGACGCAGAAACAATGATGTATGAAAAAATCAGCGGCGGTGAAGAAGAATGGC GCGTACATTTAGTGCAAGCCGTACAAGCCGGGATG GAAAAGGAAGAATTGTTCACTTTT ACGAACAGACTCAAGAAAGAACAGCCTGAAACTG CCTCTTACCGCAACCGCAAACTGA 30 CGGAATCCAATATAGAAGAATGGAAAGCGCTGATG GCGGAGGCAAGAGAAATCGGCTT GTCTGTCCATGAAGTCAAATCCTTTTTAAAAACAAAGGGAAGA SEQ ID NO 3 000000 DDD On MIGRIIRLYRKRKGYSINQLAVESGVSKSYLSKIERGVHTN PSVQFLKKVSATLEVELTELF DAETMMYEKISGGEEEWRVHLVQAVQAGMEKEELFTFT NRLKKEQPETASYRNRKLTES NIEEWKALMAEAREIGLSVHEVKSFLKTKGR SEQ ID NO 4 f 40
97. GMRSOTOLSLVKEGYNMRVYLPYGEDWYGYFMRRLAERPSNIAFAFK GMTKK SEG ID NO 53 DI DI CJ 0 0000 ATGACAACACCTTACAAACACGAGCCATTCACAAATTTCCAAGATCAAAACTACGTGG AAGCGTTTAAAAAAGCGCTTGCGACAGTAAGCGAATATTTAGGAAAAGACTATCCGCT TGTCATTAACGGCGAGAGAGTGGAAACGGAAGCGAAAATCGTTTCAATCAACCCAGC TGATAAAGAAGAAGTCGTCGGCCGAGTGTCAAAAGCGTCTCAAGAGCACGCTGAGC AAGCGATTCAAGCGGCTGCAAAAGCATTTGAAGAGTGGAGATACACGTCTCCTGAAG AGAGAGCGGCTGTCCTGTTCCGCGCTGCTGCCAAAGTCCGCAGAAGAAAACATGAA TTCTCAGCTTTGCTTGTGAAAGAAGCAGGAAMAGCCTTGGAACGAGGCGGATGCCGAT ACGGCTGAAGCGATTGACTTCATGGAGTATTATGCACGCCAAATGATCGAACTGGCA AAAGGCAAACCGGTCAACAGCCGTGAAGGCGAGAAAAACCAATATGTATACACGCCG ACTGGAGTGACAGTCGTTATCCCGCCTTGGAACTTCTTGTTTGCGATCATGGCAGGC ACAACAGTGGCGCCGATCGTTACTGGAAACACAGTGGTICTGAAACCTGCGAGTGCT ACACCTGTTATTGCAGCAAAATTTGTTGAGGTGCTTGAAGAGTCCGGATTGCCAAAAG GCGTAGTCAACTTTGTTCCGGGAAGCGGATCGGAAGTAGGCGACTATCTTGTTGACC ATCCGAAAACAAGCCTTATCACATTTACGGGATCAAGAGAAGTTGGTACGAGAATTTT CGAACGCGCGGCGAAGGTTCAGCCGGGCCAGCAGCATTTAAAGCGTGTCATCGCTG AAATGGGCGGTAAAGATACGGTTGTTGTTGATGAGGATGCGGACATTGAATTAGCGG CTCAATCGATCTTTACTTCAGCATTCGGCTTTGCGGGACAAAAATGCTCTGCAGGTTC ACGTGCAGTAGTTCATGAAAAAGTGTATGATCAAGTATTAGAGCGTGTCATTGAAATT ACGGAATCAAAAGTAACA
98. GTATTTAGAAAAAT AAACAAATAGG GGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTCCAATAGACCAGTTGCAATCCAAA CGAGAGTCTAATAGAATGAGGTCGAAAAGTAAATCGCGTAATAAGGTAATAGATTTACATTAGA AAATGAAAGGGGATTTTATGCGTGAGAATGTTACAGTCTATCCCGGCATTGCCAGTCGGGGAT ATTAAAAAGAGTATAGGTTTTTATTGCGATAAACTAGGTTTCACTTTGGTTCACCATGAAGATGG ATTCGCAGTTCTAATGTGTAATGAGGTTCGGATTCATCTATGGGAGGCAAGTGATGAAGGCTG GCGCTCTCGTAGTAATGATTCACCGGTTTGTACAGGTGCGGAGTCGTTTATTGCTGGTACTGC TAGTTGCCGCATTGAAGTAGAGGGAATTGATGAATTATATCAACATATTAAGCCTTTGGGCATT TTGCACCCCAATACATCATTAAAAGATCAGTGGTGGGATGAACGAGACTTTGCAGTAATTGATC CCGACAACAATTTGATTACAAATAAAAAGCTAAAATCTATTATTAATCTGTTCCTGCAGGAGAGA CCG 1 J J 10 20 30 50 90 JP 2007 532114 A 2007 11 15
99. GTCA 194 SgDDF Ee GCGGCGARTTCTCTGCTGGARAAAGTGATACA 185 sor Now TICGOTGOGATARCEACAT s tpeUF Bali 5 LepsDR EGRI GCGSCGAATTCATATEGCEGCOGCATARCTIC 1 sw Wee Eee SoDDO None GAATAGGMTACECASTTO NS EE ScOR None CTCCTGATCCARACATGTAAG TT W 30 RT sigD 7 183 186 188 189 190 191 92 86 JP 2007 532114 A 2007 11 15 8 prpC 7 2 7 p115 GATCTTCACCCTCTTCAACTTGTAAAG anal PCR A Ea meses ZE p95 GCGCCCTTGATCCTAAGTCAGATGAAAC p96 UR CGGGTCCGATACTGACTGTAAGTTTGAC d EE PflMI GTACCATAACCATGCCTTGGTTAGGATGCATATGGCGGCCGC 195 p101 CCTTGTCTTCCATCTTGCTGGAGCTGGATCCATAACTTCGTATAATG p114 None GAGAGCAAGGACATGACATTGACGC 197
100. HHHHHH JP 2007 532114 A 2007 11 15 40 10 20 30 50 HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 41 JP 2007 532114 A 2007 11 15 00000000 UU ATGAAAAAAGCTG TCATTGTAGAAAACAAA
101. HHHHHHH UI IU 20 30 JP 2007 532114 A 2007 11 15 21 O O 10 20 30
102. HHHHHHHHHH iQ U HHHHHHHHHHH O HHHHHHHHHHH DO i U HHHHHHHHHHH ii AO O o HN A A E GR LA u iii 140000000056 ig U U HHHHHHHHHHH ii Odd U HHHHHHHHHHH HHHHHHHHHHH 10 20 30 50 JP 2007 532114 A 2007 11 15 69 10 20 HHHHH 30 50 DU OO 00 O On DU
103. JP 2007 532114 A 2007 11 15 19 JP ON RR RA SA 11 2007 532114 P2007 532114A 43 19 11 15 2007 11 15 51 Int 01 F 1 C12N 15 09 2006 01 C12N 15 00 ZNAA 4B024 C12N 1 21 2006 01 C12N 1 21 4BO50 C12N 9 56 2006 01 C12N 9 56 4B063 C12N 15 01 2006 01 C12N 15 00 x 4BO65 C12Q 1 68 2006 01 C12N 15 00 F BERK KAR IR 26 51 KR 104 A 21 2007 507507 P2007 507507 71 500284580 86 22 17 4 7 2005 4 7 85 18 12 11 2006 12 11 2 86 PCT US2005 011821 87 02006 033668 925 87 18 3 30 2006 3 30 74 100071010 31 60 561 110 32 16 4 9 2004 4 9 74 100121762 33 US 74 100126767 74 100118647 74 100138519 REL
104. KESAYLIQNIFENKSSSSALSITAFNAGAAIYTAGIT ASLKEGTELALETITSGGAAAQLERLKQKEEEIYA SEQ ID NO 47 00000060 HHHHHHHHHHHHHHHHHHHHHHH 10 20 30 59 JP 2007 532114 A 2007 11 15 T D MNFQSNISAFLEDSLSHHTIPIVETFTVDTLTPIQMIEKLDREITYLLESKDDTSTWSRY SFIGLNPFLTIKEEQGRESAADQDSKSLYTGNELKEVLNWMNTTYKIKTPELGIPFVGGA VGYLSYDMIPLIEPSVPSHTKETDMEKCMLFVCRTLIAYDHETKNVHFIQYARLTGEETK NEKMDVFHQNHLELQNLIEKMMDQKNIKELFLSADSYKTPSFETVSSNYEKSAFMADVEK IKSYIKAGDIFQGVLSQKFEVPIKADAFELYRVLRIVNPSPYMYYMKLLDREIVGSSPERLIH VQDGHLEIHPIAGTRKRGADKAEDERLKVELMKDEKEKAEHYMLVDLARNDIGRVAEYG SVSVPEFTKIVSFSHVMHIISVVTGRLKKGVHPVDALMSAFPAGTLTGAPKIRAMQLLQEL EPTPRETYGGCIAYIGFDGNIDSCITIRTMSVKNGVASIQAGAGIVADSVPEAEYEESCNKA GALLKTIHIAEDMFHSKEDKADEQISTIVR SEQ ID NO 49 10000 1000000000 IU go 1000 MKKPALKYCGIRSLKDLQLAAESQADYLGFIFAESKRKVSPEDVKKWLNQVRVEKQVAG VFVNESIETMSRIAKSLKLDVIQLHGDEKPADVAALRKLTGCEIWKALHHQDNTTQEIARF KDNVDGFVIDSSVKGSRGGTGVAFSWDCVPEYQQAAIGKRCFIAGGVNPDSITRLLKWQ PEGIDLASGIEKNGQKDQNLMRLLEERMNRYVSISE SEQ ID NO 51 1 DU
105. TGAAGACGGTACGCGACTGGGCGTGGAGCATCTGGTCGCATTGGGTCACC AGCAAATCGCGCTGTTAGCGGGCCCATTAAGTICTGTCTCG GCGCGTCTGCGTCTGGCTGGC TGGCATAAATATCTCACTCGCAATCAAATTCAGCCGATAGCG GAACGGGAAGGCGACTGGAGT GCCATGTCCGGTTTTCAACAAACCATGCAAATGCTGAATGAGGGCATCGTTCCCACTGCGATG CTGGTTGCCAACGATCAGATGGCGCTGG GCGCAATGCGCGCCATTACCGAGTCCGGGCTGC GCGTTGGTGCGGATATCTCGGTAGTGGGATACGACGATACCGAAGACAGCTCATGTTATATCC CGCCGTCAACCACCATCAAACAGGATTTTCG CCTGCTGGGGCAAACCAGCGTGGACCGCTTG 10 20 30 89 JP 2007 532114 A 2007 11 15 O CTGCAACTCTCTCAGGGCCAGGCGGTGAAGGGCAATCAGCTGTTGCCCGTCTCACTGGTGAA AAGAAAAACCACCCTGGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCAT TAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAA TGTGAGTTAGGCATCGCATCCTGCCTCGCGCGTTTCGGTGATGACGGTGAAAACCTCTGACAC ATGCAGCTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGGATGCCGGGAGCAGACAAGCCC GTCAGGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGGCGCAGCCATGACCCAGTCACGTAG CGATAGCGGAGTGTATACTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGTGCAC CATATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCGCTCTTCC GCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCA CTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAG CAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGG CTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGAC AGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGAC CCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCAATG CTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTC
106. TTTATGTTAAAGTGAAAAAAACA GATGTTGGGAGGTACAGTGATAGTTGTAGATAGAAAAGAAGAGAAAAAAGTTG CTGTTACTTTA AGACTTACAACAGAAGAAAATGAGATATTAAATAGAATCAAAGAAAAATATAATATTAGCAAATC AGATGCAACCGGTATTCTAATAAAAAAATATGCAAAGGAGGAATACGGTG CATTTTAAACAAAA AAAGATAGACAGCACTGG CATGCTGCCTATCTATGACTAAATTTT GTTAAGTGTATTAGCACCG TTATTATATCATGAGCGAAAATGTAATAAAAGAAACTGAAAACAAGAAAAATTCAAGAGGACGT AATTGGACATTTGTTTTATATCCAGAATCAGCAAAAG CCGAGTGGTTAGAGTATTTAAAAGAGT TACACATTCAATTTGTAGTGTCTCCATTACATGATAGGGATACTGATACAGAAGGTAGGATGAA AAAAGAGCATTATCATATTCTAGTGATGTATGAGGGTAATAAATCTTATGAACAGATAAAAATAA TTAACAGAAGAATTGAATGCGACTATTC CGCAGATTGCAGGAAGTGTGAAAGGTCTTGTGAGA TATATGCTTCACATGGACGATCCTAATAAATTTAAATATCAAAAAGAAGATATGATAGTTTATGG CGGTGTAGATGTTGATGAATTATTAAAG AAAACAACAACAGATAGATATAAATTAATTAAAGAAA TGATTGAGTTTATTGATGAACAAGGAATCGTAGAATTTAAGAGTTTAATGGATTATGCAATGAAG TTTAAATTTGATGATTG GTTCCCGCTTTTATGTGATAACTCGGCGTATGTTATTCAAGAATATAT AAAATCAAATCGGTATAAATCTGACCGATAGATTTTGAATTTAGGTGTCACAAGACACTCTTTTT TCGCACCAGCGAAAACTGGTTTAAGCCGACTGGAGCTCCTGCACTGGATGGTGG CGCTGGAT GGTAAGCCG CTGGCAAGCGGTGAAGTGCCTCTGGATGTCGCTCCACAAGGTAAACAGTTGAT TGAACTGCCTGAACTACCGCAGCCGGAGAGCGCCGGGCAACTCTGGCTCACAGTACGCGTAG TGCAACCGAACGCGACCGCATGGTCAGAAGCCGGGCACATCAGCGCCTGGCAGCAGTGGCG TCTGGCGGAAAACCTCAGTGTGACGCTCCCCGCCGCGTCCCACG CCATCCCGCATCTGACCA CCAGCGAAATGGATTTTTGCATCGAGCTGGGTAATAAGCGTTGGCAATTTAACCGCCAGTCAG GCTTTCTTTCACAGATGTGGATTGGCGATAAAAAACAACTGCTGACGCCGCTGCGCGATCAGT TCACCCGTGCACCGCTGGATAACGACATTGGCGTAAGTGAAGCGACCCGCATTGACCCTAAC GCCTGGGTCGAACGCTGGAAG
107. TTTGTATTATCAGCC TGCCATGAAACGATCGGATAATGCCGGACTAAAAACAGCATTGGCAAGAGCTGTGATG TACGATACGGTTATTCAGCATGGCGATGGTGATGACCCTGACTCTTTTTATGCCTTGAT TAAACGTACGAACAAAAAAGCGGGCGGATCACCTAAAGACGGAATAGACGAGAAGAAG TGGTTGAATAAATTCTTGGACGTACGCTATGACGATCTGATGAATCCGGCCAATCATGA CACCCGTGACGAATGGAGAGAATCAGTTGCCCGTGTGGACGTGCTTCGCTCTATCGCC AAGGAGAACAACTATAATCTAAACGGACCGATTCATGTTCGTTCAAACGAGTACGGTAA TTTTGTAATCAAA SEQ ID NO 7 44 JP 2007 532114 A 2007 11 15 10000 MKISMQKADFWKKAAISLLVFTMFFTLMMSETVFAAGLNKDQKRRAEQLT YGYVERLDDGRGYTCGRAGFTTATGDALEVVEVYTKAVPNNKLKIKYLPELRRLAKEESD DTSNLKGFASAWKSLANDKEFRAAQDKVNDHLYYQPAMKRSDNAGLKTALARAVMYDT VIQHGDGDDPDSFYALIKRTNKKAGGSPKDGIDEKKWLNKFLDVRYDDLMNPANHDTRD EWRESVARVDVLRSIAKENNYNLNGPIHVRSNEYGNFVIK SEQ ID NO 8 EE E JE JAVA IN OU ERI 00000 00000 HHHHHHHHHHHHHHHHHHHHHH n ATGAAAAGAAACCAAAAAGAATGGGAATCTGTGAGTAAAAAAGGACTTATGAAGCCGG GAGGTACTTCGATTGTGAAAGCTGCTGGCTGCATGGGCTGTTGGGCCTCGAAGAGTAT TGCTATGACACGTGTTTGTGCACTTCCGCATCCTGCTATGAGAGCTATT SEQ ID NO 5 10000 MKRNQKEWESVSKKGLMKPGGTSIVKAAGCMGCWASKSIAMTRVCALPHPAMRAI SEQ ID NO 6 8
108. U 100000 10000000 B 100000 HHHHHHHLH D 100000000 000000 HHHHHHHLH 10 20 30 50 JP 2007 532114 A 2007 11 15 8 D D D n 10 20 30 IU o O 0000 di sabli ef D D VHONG
109. VAKGKARI 30 RTIITAEHTKDELDQALDVIEKTAKELQLL SEQ ID NO 26 1 1000000 n H n n n 50 JP 2007 532114 A 2007 11 15 ATGAACTCAGTTGATTTGACCGCTGATTTACAAG CCTTATTAACATGTCCAAATGTGC GTCATAATTTATCAG CAGCACAGCTAACAGAAAAAGTCCTCTCCCGAAACGAAGGCAT TTTAACATCCACAGGTGCTGTTCGCGCGACAACAGGCGCTTACACAGGACG CTCACC TAAAGATAAATTCATCGTGGAGGAAGAAAGCACGAAAAATAAGATCGATTGGGGCCC GGTGAATCAGCCGATTTCAGAAGAAGCGTTTGAGCGGCTGTACACGAAAGTTGTCAG CTATTTAAAGGAGCGAGATGAACTGTTTGTTTTCGAAGGATTTGCCGGAGCAGACGA GAAATACAGGCTGCCGATCACTGTCGTAAATGAGTTCGCATGGCACAATTTATTTGCG CGGCAGCTGTTTATCCGTCCGGAAGGAAATGATAAGAAAACAGTTGAGCAGCCGTTC ACCATTCTTTCTGCTCCGCATTTCAAAGCGGATCCAAAAACAGACGGCACTCATTCCG AAACGTTTATTATTGTCTCTTTCGAAAAGCGGACAATTTTAATCGGCGGAACTGAGTA TGCCGGTGAAATGAAGAAGTCCATTTTCTCCATTATGAATTTCCTGCTGCCTGAAAGA GATATTTTATCTATGCACTGCTCCGCCAATGTCGGTGAAAAAGGCGATGTCGCCCTIT TCTTCGGACTGTCAGGAACAGGAAAGACCACCCTGTCGGCAGATGCTGACCGCAAG CTGATCGGTGACGATGAACATGGCTGGTCTGATACAGGCGTCTTTAATATTGAAGGC GGATGCTACGCTAAGTGTATTCATTTAAG CGAGGAAAAGGAGCCGCAAATCTTTAAC GCGATCCGCTTCGGGTCTGTTCTCGAAAATGTCGTTGTGGATGAA
110. VPK SEQ ID NO 18 46 JP 2007 532114 A 2007 11 15 MA O AA 4 0 01 NU NAO D DEO DA HOIN D EI ZI HHHHHHHHHHHHH ATGTTTAAAAATAATGTCATACTTTTAAATTCACCTTATCATGCACATGCTCATAAAGA GGGGTTTATTCTAAAAAGGGGATGGACGGTTTTGGAAAGCAAGTACCTAGATCTACT CGCACAAAAATACGATTGTGAAGAAAAAGTGGTAACAGAAATCATCAATTTGAAAGCG ATATTGAACCTGCCAAAAGGCACCGAGCATTTTGTCAGTGATCTGCACGGAGAGTAT CAGGCATTCCAGCACGTGTTGCGCAATGGTTCAGGACGAGTCAAAGAGAAGATACG CGACATCTTCAGCGGTGTCATTTACGATAGAGAAATTGATGAATTAGCAGCATTGGTC TATTATCCGGAAGACAAACTGAAATTAATCAAACATGACTTTGATGCGAAAGAAGCGT TAAACGAGTGGTATAAAGAAACGATTCATCGAATGATTAAGCTCGTTTCATATTGCTC CTCTAAGTATACCCGCTCCAAATTACGCAAAGCACTGCCTGCCCAATTTGCTTATATT ACGGAGGAGCTGTTATACAAAACAGAACAAGCTGGCAACAAGGAGCAATATTACT CC GAAATCATTGATCAGAT CATT GAACTTGGCCAAGCCGATAAGCTGATCACCGGCCTT GCTTACAGCGTTCAGCGATTGGTGGTCGACCATCTGCATGTGGTCGGCGATATTTAT GACCGCGGCCCGCAGCCGGATAGAATTATGGAAGAACTGATCAACTATCATTCTGTC GATATTCAGTGGGGAAATCACGATGTCCTTTGGATCGGCGCCTATTCCGGTTCCAAA GTGTGCCTGGCCAATATTATCCGCATCTGTGCCCGCTACGACAACCTGGATATTATTG AGGACGTGTACGGCATCAACCTGAGACCGCTGCTGAACCTGGCCGAAAAATATTATG ATGATAATCCAGCGTTCCGTCCAAAAGCAGACGAAAACAGGCCAGAGGATGAGATTA AGCAAATCACAAAAATCCATCAAGCGATTGCCATGATCCAATTCAAGCTTGAGAGCCC GATTATCAAGAGACGGCCGAACTTTAATATGGAAGAGCGGCTGTTATTAGAGAAAATA GACTATGACAAAAATGAA
111. ent in particular paragraph 0012 WO 03 070963 A GENENCOR INTERNATIONAL INC BRON SIERD FERRARI EUGENIO TJALSMA H 28 August 2003 2003 08 28 103 JP 2007 532114 A 2007 11 15 S INTERNATIONAL SEARCH REPORT Information on patent family members WO 03083125 A 09 10 2003 AU CA 2003228393 Al 2480277 Al 1495128 Al 2005521407 T international application No PCT US2005 011821 0 13 10 2003 09 10 2003 12 01 2005 21 07 2005 US 2002065403 Ai 30 05 2002 AT A 338133 T 6410400 A 0004957 A 2322555 Al 1308125 A 19950409 Al 1094111 A2 0004115 A2 27693 A 2001149086 A PA00009958 A 343339 A1 15292000 A3 200005843 A 15 09 2006 26 04 2001 29 05 2001 20 04 2001 15 08 2001 26 04 2001 25 04 2001 28 09 2002 26 04 2001 05 06 2001 28 04 2005 23 04 2001 03 12 2001 17 05 2001 tr F n EP 0723011 B 03 07 2002 A 220099 T 682547 B2 8099194 A 9407625 A 2169170 Al 1133615 A 9600524 A3 69430919 01 69430919 T2 0723011 Al 73690 A2 9506114 Ai 313119 Ai 20496 A3 5876983 A 5919694 A 15 07 2002 09 10 1997 21 03 1995 21 01 1997 02 03 1995 16 10 1996 12 06 1996 08 08 2002 27 02 2003 24 07 1996 30 09 1996 02 03 1995 10 06 1996 06 11 1996 02 03 1999 06 07 1999 US 2004241831 Al 02 12 2004 2004225550 Al 10409192 A 1768132 A 1611232 Al 2006521789 T 2004087895 Al PAO5010725 A 14 10 2004 11 04 2006 03 05 2006 04 01 2006 28 09 2006 14 10 2004 15 12 2005 WO
112. icular relevance the clalmed invention Ting date cannol be novel or cannot be considered 10 ut document KO throw doubts on dedi or Involve an Inventive step when the document ks taken alone 2 pu Y document of particular relevance the claimed invention dilation or other special reason as apecltiad cannot be considered lo involve an inventive Btep when the O document referring to an oral disclosure use exhibition or document ls combined with one or more other such docu athar means Such combination being obvious to a person skilled P document published prior to the international filing data but in Ihe art later than the priority date clalmed amp document member of the same patent family Date of the actual completion of the internatjonal search Date af malling of the Intemational search report 21 August 2006 01 12 2006 Nama and mailing address of the ISA Authorized officer European Patent Office P B 6818 Palentiaan 2 Tel 31 70 340 2040 Tx 31 651 epo ni Fax 31 70 340 3018 Basstas Ioannis For PCTASA 210 second sheet April 2005 16 3 2007 100 JP 2007 532114 A 2007 11 15 2 International application No INTERNATIONAL SEARCH REPORT PCT US2005 011821 Box H Observations where certain claims were found unsearchabie Continuation of item 2 of first sheet This Intemational Search Report has not been established in respect of certaln claims under Article 17 2 a for the following
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