Aureo_00040 : CDS information

close this sectionLocation

Organism
StrainHKI-227
Entry nameAureothin
Contig
Start / Stop / Direction5,990 / 11,710 / + [in whole cluster]
5,990 / 11,710 / + [in contig]
Location5990..11710 [in whole cluster]
5990..11710 [in contig]
TypeCDS
Length5,721 bp (1,906 aa)
Click on the icon to see Genetic map.

close this sectionAnnotation

Category1.1 PKS
Productpolyketide synthase
Product (GenBank)polyketide synthase type I
Gene
Gene (GenBank)aurA
EC number
Keyword
  • iterative
Note
Note (GenBank)
Reference
ACC
PmId
[14700630] Iteration as programmed event during polyketide assembly; molecular analysis of the aureothin biosynthesis gene cluster. (Chem Biol. , 2003)
[15812854] Functional analysis of the aureothin iterative type I polyketide synthase. (Chembiochem. , 2005)
[22799266] Interchenar retrotransfer of aureothin intermediates in an iterative polyketide synthase module. (J Am Chem Soc. , 2012)
[23606628] Multifactorial control of iteration events in a modular polyketide assembly line. (Angew Chem Int Ed Engl. , 2013)
comment
[PMID: 14700630](2003)
aureothin生合成gene clusterの同定論文。

AurA: polyketide synthase(module 1)

詳細な配列解析と、aureothin生合成遺伝子フルセットの異種性発現から、5つの伸長・還元サイクルの触媒に4つのPKS modulesで十分であるということが証明された。module構造とAT基質特異性から、aureothin PKSの最初のmuduleであるAurAが2回使用されるということが強く示唆された。

---
[PMID: 15812854](2005)
反復性質についての続報。
AurAB fusion proteinの異種性発現により、AurAの反復性質を証明。

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[PMID: 22799266](2012) abstract
反復性質についての続報。
PKS moduleの反復利用について、domain不活化解析から推定。
AurAのN末は反復過程に関与しない。

---
[PMID:23606628](2013)
反復性質についての続報。

truncated mutantをテストし、AurAのN末(ACP)はaureothin PKSのprimingに必須でないことがわかった。

AurAのN末にあるACP+KS1をavermectionのAT+ACP+KS1に変更したmutantは、starterにL-isoleucine由来2-methylbutyrate unitを取り込み、鎖伸長で反復のないaverpyroneを産生した。よって、AurAのKS1 domainは反復現象で重要な役割を果たす。

TEを削除して中間体を検出。AurA and AurBの中間体は予想通りのものが検出され、長い骨格や短い骨格の代謝産物は産生されなかった。

aurA and aurEをS. lividans ZX1に導入した株にPNBAの補充して得られたpolykeidesは、di- and triketide中間体に加え、最高4ラウンドの伸長に由来するものも検出された。

総合すれば、KS1は明らかに反復を媒介するが、下流のmodule 2(KS2)がaureothin polyketide骨格の正しい組み立てを調節するgatekeeperとして役立つ。

close this sectionPKS/NRPS Module

0
1 methylmalonyl-CoA
ACP19..96
KS116..490
AT648..966
DH1015..1177
KR1497..1676
ACP1783..1853

close this sectionSequence

selected fasta
>polyketide synthase [polyketide synthase type I]
MELHEGGDRSLRERLSAAREADRHRLLLDLIRTHSATATDGRARALDAGRAFGEQGVRGK
SAGKLRELLSEATGLALSATVVFDYPTPRALAEHLTGLLLGEDTAGPAAAAAAAADEPIA
IVGMGCRLPGGVNSPEGLWELVRSETDAISEFPTDRGWDVEYDPDPDHIGTTVTRHAGFL
YEAPDFDADFFAISPGEAVTIDPQHRLLLETTWEAIEGARLDPTSLRGSRTGVFVGLMYS
EYGARIRNVPPAAEGYRVVGSMPSVASGRLAYTFGFEGPAVTVDTACSSSLVAMHLAAES
LRKGECSLAVAGGATVMSTPWGYIEFSRQRGLAPDGRARSFSADAAGSSWSEGVGVVVLE
RLSDARRNGHRVLAVLRGSAVNQDGASNGLTAPNGPAQQQVIRQALVHAGLSTADVDVVD
AHGAGTRLGDPIEAQALLATYGQGRPADQPLWLGSLKSNIGHTQAAAGVSGVIKMVMAIR
NGVLPRSLHITEPTPVVDWSSGAVELLTEARPWPEAGRPRRAGVSSFGVGGTNAHVILEQ
AEPEPDPAPASDGDGDARPLPWLVSGRGAAGLRAQAGRIRAFLEAHPEVPDADVAYSLAA
TRAALPDRAVVVAADRAEAVARLAALADGEQGEQVALGVAANRDRLAFVFPGQGSQWPGM
AAELMSTSPVFRESIEACEKSLAPYVDWSLTKVLRGRSGAPTLERVDVVQPALFAVMVSL
AALWRSFGVEPAAVVGHSQGEIAAAHVAGALSLDDAARIVAVRSKALRVLSGRGGMVSVA
APVDRVLRELERWDGSVSVAAVNGPRAVVISGDPTGLDEAIEAFTADGLRAKKIPVDYAS
HSAQVEEIRETLRETLAGIAPRRSEVPFYSTVTGEPVDTTILDTEYWITNLRETVQFDRT
VRRLIDDGHTGFVEMSPHPVLTVGVQETIDDVAADGVLTFDSLRRNEGGTARLLTALGEA
HAHGIPVDWAQVFDHAGPRPVDLPTYAFQRRRYWLEEAAAPEADLASAGLDGVDHPLLGA
AVSLPDGGTLFTGTLSARTHPWLTDHGVADVLVVPGTALVDLALHAGGQTGCEVLEELVL
HAPLILPEQDTVRVQLALGAPDESGRRSVTVHARSGEARSDDPWTLHAEGTLARDGERSE
DLPQAWPPAGAEEIELDDCYRQLAKNGLHYGAAFQGLKRGWRLDGDVFVEVELPESGGPA
GGYGLHPALFDAALHAAAFVGLPGAAADDAVTRLPFSWSGVALHATGAVRLRARIRFTGP
ESLSVTAADPTGRPVVTIASLGMRPVTAEALHRAAASAGTSLLRLEWQPAARPAPRALDE
ERWVWIGNGAPGGQFERHDEPAGLRAALDAGATAPDVVVLAELPAAGDAADADTLGAAHR
AVHRVLAAVQDWSADDRLAASRLVVLTRDAVATASDAVPAPVLAAVWGLIRSAQAENPGR
IVLVDLDGRDESLAALPSALDTGEAQLAVRDGALLVPRLARVTTPGDRGAVALRTDGTVL
VTGGLGVLGRLVVRHLVTAHGIRRVLVVSRSGGTGEGVADFTAELNAEGAELHVVAGDAA
DRAVLEGALASIPAEHPLTAVVHMAGVLDDGVLTSLTPERADRVLRPKADAAWHLHELTA
GQDVPLVVFSSLSSVLGPAGQGSYAAANAFVDALVERRRAAGSPGVALGWGLWGARSGLT
GDLDEADLRRMARTGVQPLSSDQGLALFDLARAGDDPVVFPLHLDTAALGGGDADDVPPV
LRGLARTPARRATVRAAEERPAGDDTLADRLARVPEAEQEAQLLTLVRSHVAAVLGYDDP
RTVGERRTFTDIGFDSLRALQLRNRLNGATGLRLPATLVFDHPTPVELGRYLRTRLVPDA
PSAPDTAEAVTPPPAAPGEGNEAMEQLRSAASLEEVFDLLDDQLGK
selected fasta
>polyketide synthase [polyketide synthase type I]
ATGGAGTTGCACGAGGGAGGCGACCGGTCGCTCCGTGAGCGGCTGTCGGCCGCTCGGGAG
GCGGATCGACACCGTCTGCTGCTCGATCTGATCCGTACCCACAGCGCCACCGCCACGGAC
GGGAGGGCCCGCGCCCTCGACGCCGGGCGGGCCTTCGGCGAGCAGGGGGTGCGCGGGAAG
TCCGCCGGGAAGCTGCGGGAGCTGCTCTCCGAGGCCACGGGCCTCGCGCTCTCCGCGACC
GTCGTCTTCGACTACCCCACCCCCCGCGCCCTCGCGGAGCACCTCACCGGCCTGCTGCTC
GGCGAGGACACCGCCGGGCCGGCCGCCGCCGCGGCAGCGGCCGCGGACGAGCCGATCGCC
ATCGTCGGCATGGGCTGCCGACTCCCCGGCGGAGTGAACTCCCCCGAGGGGCTCTGGGAG
TTGGTGCGCTCCGAGACGGACGCGATCTCCGAGTTCCCCACCGACCGCGGCTGGGACGTC
GAGTACGACCCGGACCCGGACCACATCGGCACGACGGTCACCCGGCACGCCGGCTTCCTC
TACGAGGCACCCGACTTCGACGCCGACTTCTTCGCGATCAGCCCCGGCGAGGCGGTGACG
ATCGACCCCCAGCACCGGCTGCTGCTGGAGACCACCTGGGAGGCCATTGAAGGGGCCCGG
CTGGACCCGACCTCGCTGCGCGGCAGCCGGACCGGCGTCTTCGTCGGCCTCATGTACAGC
GAGTACGGTGCCCGGATCCGCAACGTGCCCCCGGCCGCGGAGGGTTACCGCGTCGTCGGC
AGCATGCCCAGCGTCGCCTCGGGCCGCCTCGCCTACACCTTCGGCTTCGAGGGCCCCGCG
GTCACCGTGGACACCGCCTGCTCGTCGTCCCTGGTGGCCATGCACCTCGCGGCCGAGTCG
CTGCGCAAGGGCGAGTGCTCGCTCGCCGTGGCCGGCGGCGCCACCGTGATGTCGACGCCC
TGGGGCTACATCGAGTTCAGCCGCCAGCGCGGCCTGGCCCCCGACGGGCGGGCCCGGTCC
TTCTCGGCGGACGCGGCCGGCAGCAGCTGGTCGGAGGGCGTGGGCGTGGTCGTGCTGGAG
CGGCTGTCCGACGCCCGGCGCAACGGGCACCGCGTGCTCGCCGTCCTGCGCGGCTCCGCG
GTCAACCAGGACGGCGCGTCCAACGGCCTGACGGCGCCCAACGGCCCGGCCCAGCAGCAG
GTGATCCGGCAGGCGCTGGTCCACGCGGGACTGTCCACGGCGGACGTGGACGTGGTCGAC
GCGCACGGCGCCGGAACGCGCCTCGGCGACCCGATCGAGGCGCAGGCGCTGCTGGCCACC
TACGGCCAGGGCCGTCCGGCGGACCAGCCGCTGTGGCTCGGCTCGCTGAAGTCCAACATC
GGCCACACCCAGGCCGCGGCCGGCGTCTCGGGCGTCATCAAGATGGTGATGGCGATCCGC
AACGGCGTCCTGCCGCGCAGCCTGCACATCACCGAGCCGACGCCGGTGGTGGACTGGTCC
TCCGGCGCGGTGGAGCTGCTGACCGAGGCCCGGCCCTGGCCCGAGGCGGGCCGGCCGCGC
CGGGCGGGCGTCTCCTCGTTCGGCGTGGGCGGGACCAACGCCCACGTCATCCTGGAGCAG
GCGGAGCCCGAGCCCGACCCGGCCCCGGCGTCCGACGGGGACGGCGACGCCCGTCCGCTG
CCCTGGCTGGTCTCCGGCCGCGGCGCCGCGGGCCTGCGCGCCCAGGCCGGCCGGATCCGT
GCGTTCCTGGAGGCCCACCCCGAGGTCCCGGACGCGGACGTGGCGTACTCGCTGGCCGCG
ACCCGGGCGGCGCTGCCGGACCGGGCCGTCGTGGTGGCCGCGGACCGCGCCGAGGCCGTC
GCGCGCCTCGCCGCCCTCGCCGACGGCGAGCAGGGCGAGCAGGTGGCGCTGGGCGTCGCG
GCGAACCGGGACCGCCTCGCCTTCGTGTTCCCCGGACAGGGCTCCCAGTGGCCGGGCATG
GCCGCCGAGCTGATGAGCACCTCACCGGTCTTCCGGGAGTCCATCGAGGCGTGCGAGAAG
AGCCTCGCCCCGTACGTGGACTGGTCGTTGACGAAGGTGCTGCGGGGCCGGTCCGGCGCG
CCGACCCTGGAACGCGTCGACGTCGTGCAGCCGGCGCTGTTCGCGGTGATGGTCTCCCTC
GCGGCGCTGTGGCGCTCCTTCGGCGTGGAACCGGCCGCGGTCGTCGGGCACTCGCAGGGC
GAGATCGCCGCGGCCCACGTCGCGGGCGCGCTCTCCCTGGACGACGCGGCCCGCATCGTC
GCCGTGCGCAGCAAGGCGCTGCGGGTCCTGTCGGGCCGCGGCGGGATGGTCTCGGTCGCC
GCCCCCGTCGACCGGGTGCTGCGCGAACTGGAGCGCTGGGACGGCTCCGTGTCGGTCGCG
GCGGTCAACGGGCCGCGCGCCGTGGTCATCTCCGGCGACCCCACGGGACTGGACGAGGCG
ATCGAGGCGTTCACCGCCGACGGTCTGCGCGCCAAGAAGATCCCGGTGGACTACGCCTCG
CACTCGGCCCAGGTCGAGGAGATCCGCGAGACCCTGCGGGAGACGCTGGCCGGCATCGCG
CCGCGCCGGTCGGAGGTGCCGTTCTACTCGACGGTGACCGGCGAGCCCGTCGACACCACG
ATCCTGGACACCGAGTACTGGATCACCAACCTCCGCGAGACCGTCCAGTTCGACCGCACC
GTCCGCCGGCTCATCGACGACGGCCACACCGGCTTCGTCGAGATGAGCCCGCACCCGGTG
CTCACCGTCGGCGTCCAGGAGACCATCGACGACGTGGCGGCCGACGGCGTCCTGACCTTC
GACTCGCTGCGGCGCAACGAGGGCGGCACGGCACGGCTGCTGACCGCGCTCGGCGAGGCC
CACGCGCACGGGATCCCCGTCGACTGGGCGCAGGTCTTCGACCACGCCGGACCGCGGCCG
GTGGACCTGCCGACCTACGCCTTCCAGCGGCGCCGCTACTGGCTGGAGGAGGCCGCCGCA
CCCGAGGCCGACCTGGCGTCGGCCGGGCTCGACGGCGTCGACCACCCCCTGCTGGGCGCC
GCCGTCTCCCTGCCGGACGGCGGGACGCTGTTCACCGGCACGCTGTCGGCCCGGACCCAC
CCCTGGCTCACCGACCACGGCGTCGCCGACGTCCTCGTCGTGCCCGGTACCGCGCTGGTG
GACCTGGCGCTGCACGCCGGCGGGCAGACGGGCTGCGAGGTGCTGGAGGAGCTGGTCCTC
CACGCGCCGCTGATCCTGCCCGAACAGGACACGGTCCGCGTCCAGTTGGCCCTCGGGGCA
CCGGACGAGTCGGGGCGGCGCTCCGTCACCGTCCACGCGCGCTCCGGCGAGGCCCGGTCC
GACGATCCGTGGACCCTGCACGCCGAGGGCACGCTGGCCCGCGACGGCGAGCGCTCCGAG
GACCTCCCGCAGGCCTGGCCGCCCGCCGGCGCCGAGGAGATCGAACTCGACGACTGCTAC
CGCCAGTTGGCCAAGAACGGGCTGCACTACGGAGCCGCGTTCCAGGGGCTGAAGCGCGGC
TGGCGCCTCGACGGGGACGTCTTCGTGGAGGTCGAGCTCCCCGAGAGCGGCGGACCGGCC
GGCGGCTACGGGCTGCACCCGGCCCTGTTCGACGCGGCGCTGCACGCCGCGGCGTTCGTC
GGCCTGCCCGGAGCGGCCGCGGACGACGCCGTGACCCGGCTGCCGTTCTCCTGGAGCGGC
GTCGCCCTGCACGCCACCGGCGCCGTCCGGCTGCGGGCCCGGATCCGCTTCACCGGACCG
GAGTCCCTGTCCGTCACCGCCGCGGACCCCACGGGCCGCCCGGTCGTCACCATCGCGTCC
CTCGGGATGCGCCCGGTGACCGCCGAGGCGCTGCACCGGGCCGCCGCCTCGGCCGGGACC
TCGCTGCTGCGCCTGGAGTGGCAGCCGGCCGCCCGGCCCGCACCCCGCGCCCTCGACGAG
GAGCGCTGGGTCTGGATCGGGAACGGCGCCCCCGGCGGGCAGTTCGAGCGCCACGACGAA
CCGGCCGGCCTGCGGGCGGCCCTGGACGCCGGCGCCACGGCGCCCGACGTCGTCGTCCTC
GCGGAGCTGCCGGCCGCCGGTGACGCCGCTGATGCCGACACGCTCGGCGCGGCGCACCGG
GCCGTCCACCGCGTCCTGGCCGCCGTCCAGGACTGGTCGGCCGACGACCGGCTCGCGGCA
TCGCGCCTGGTGGTGCTGACGCGCGACGCGGTCGCGACCGCGTCCGACGCCGTGCCGGCC
CCCGTGCTCGCCGCGGTGTGGGGCCTGATCAGGTCCGCCCAGGCGGAGAACCCGGGCCGC
ATCGTCCTGGTGGACCTCGACGGGCGCGACGAGTCCCTGGCCGCCCTGCCCTCCGCCCTG
GACACCGGGGAGGCGCAGCTCGCGGTGCGCGACGGCGCCCTCCTCGTCCCGCGCCTGGCG
CGCGTGACCACACCGGGGGACCGGGGTGCCGTGGCCCTGCGCACGGACGGCACGGTGCTG
GTGACCGGCGGACTCGGCGTGCTGGGCCGGCTGGTGGTGCGCCACCTGGTCACCGCGCAC
GGCATCCGGCGCGTCCTGGTCGTCTCCCGCTCCGGCGGCACCGGCGAGGGCGTGGCCGAC
TTCACCGCCGAACTGAACGCCGAGGGCGCCGAGTTGCACGTCGTGGCCGGGGACGCGGCG
GACCGCGCCGTACTGGAAGGGGCGTTGGCCTCGATCCCGGCGGAGCATCCGCTGACGGCC
GTGGTGCACATGGCCGGTGTGCTGGACGACGGCGTGCTGACGTCGCTGACCCCGGAGCGC
GCCGACCGCGTGCTGCGCCCCAAGGCGGACGCGGCGTGGCACCTGCACGAGCTGACCGCC
GGGCAGGACGTGCCGCTCGTGGTGTTCTCGTCGCTGTCGAGCGTGCTCGGGCCCGCCGGC
CAGGGCAGCTACGCGGCCGCGAACGCCTTCGTGGACGCCCTGGTGGAACGGCGCCGGGCC
GCCGGCTCGCCCGGTGTGGCCCTGGGCTGGGGCCTGTGGGGCGCCCGGTCGGGGCTGACC
GGCGACCTGGACGAGGCGGACCTGCGGCGCATGGCCCGGACCGGCGTCCAGCCGCTCTCC
AGCGACCAGGGACTCGCCCTGTTCGACCTCGCCCGCGCCGGCGACGACCCGGTCGTCTTC
CCGCTGCACCTGGACACCGCCGCCCTCGGCGGCGGCGACGCGGACGACGTCCCGCCCGTG
CTGCGCGGACTCGCCCGCACCCCGGCGCGGCGCGCCACCGTCCGCGCCGCGGAGGAGCGG
CCCGCGGGCGACGACACCCTGGCCGACCGCCTGGCCCGCGTGCCGGAGGCCGAACAGGAG
GCCCAGCTGCTGACGTTGGTCCGCAGCCATGTGGCGGCCGTGCTCGGCTACGACGATCCG
CGGACCGTCGGCGAGCGCCGCACGTTCACCGACATCGGCTTCGACTCGCTGCGCGCTCTG
CAGCTGCGCAACCGGCTCAACGGCGCCACGGGACTGCGCCTGCCGGCCACGCTGGTCTTC
GACCACCCCACCCCCGTCGAGCTCGGCCGCTACCTGCGGACCCGGCTCGTACCGGACGCG
CCGTCGGCGCCGGACACCGCGGAGGCGGTGACGCCGCCCCCCGCGGCGCCGGGCGAGGGG
AACGAGGCCATGGAACAGCTCCGTTCCGCGGCCTCCCTGGAAGAGGTCTTCGACCTCCTC
GACGACCAGCTCGGCAAGTAG
[0] ACP19..96
[1] KS116..490
[1] AT648..966
[1] methylmalonyl-CoA838..842
[1] DH1015..1177
[1] KR1497..1676
[1] ACP1783..1853
[0] ACP55..288
[1] KS346..1470
[1] AT1942..2898
[1] methylmalonyl-CoA2512..2526
[1] DH3043..3531
[1] KR4489..5028
[1] ACP5347..5559

close this sectionFeature

BLASTP
Database:UniProtKB:2011_09
show BLAST table
InterPro
Database:interpro:38.0
IPR001227 Acyl transferase domain (Domain)
 [640-770]  2.79999999999994e-77 G3DSA:3.40.366.10 [838-956]  2.79999999999994e-77 G3DSA:3.40.366.10
G3DSA:3.40.366.10   Ac_transferase_reg
IPR006162 Phosphopantetheine attachment site (PTM)
 [1811-1826]  PS00012
PS00012   PHOSPHOPANTETHEINE
IPR009081 Acyl carrier protein-like (Domain)
 [20-133]  3.30000526807186e-18 SSF47336 [1775-1870]  6.90001478563507e-22 SSF47336
SSF47336   ACP_like
 [27-98]  3.90000000000001e-31 G3DSA:1.10.1200.10 [1782-1856]  3.90000000000001e-31 G3DSA:1.10.1200.10
G3DSA:1.10.1200.10   ACP_like
 [19-96]  PS50075 [1783-1853]  PS50075
PS50075   ACP_DOMAIN
 [1787-1852]  3.3e-12 PF00550
PF00550   PP-binding
IPR013968 Polyketide synthase, KR (Domain)
 [1497-1674]  1.2e-52 PF08659
PF08659   KR
IPR014030 Beta-ketoacyl synthase, N-terminal (Domain)
 [116-365]  5.20000000000001e-89 PF00109
PF00109   ketoacyl-synt
IPR014031 Beta-ketoacyl synthase, C-terminal (Domain)
 [373-490]  5.59999999999999e-46 PF02801
PF02801   Ketoacyl-synt_C
IPR014043 Acyl transferase (Domain)
 [648-966]  1.5e-108 PF00698
PF00698   Acyl_transf_1
IPR016035 Acyl transferase/acyl hydrolase/lysophospholipase (Domain)
 [645-947]  3.89999861795218e-71 SSF52151
SSF52151   Acyl_Trfase/lysoPlipase
IPR016036 Malonyl-CoA ACP transacylase, ACP-binding (Domain)
 [772-837]  2.90000354677981e-18 SSF55048
SSF55048   Malonyl_transacylase_ACP-bd
IPR016038 Thiolase-like, subgroup (Domain)
 [119-377]  1.10000000000001e-87 G3DSA:3.40.47.10 [378-543]  2.1e-64 G3DSA:3.40.47.10
G3DSA:3.40.47.10   Thiolase-like_subgr
IPR016039 Thiolase-like (Domain)
 [109-543]  1.3000049540733e-95 SSF53901
SSF53901   Thiolase-like
IPR016040 NAD(P)-binding domain (Domain)
 [1496-1674]  3.60000000000001e-29 G3DSA:3.40.50.720
G3DSA:3.40.50.720   NAD(P)-bd
IPR018201 Beta-ketoacyl synthase, active site (Active_site)
 [278-294]  PS00606
PS00606   B_KETOACYL_SYNTHASE
IPR020801 Polyketide synthase, acyl transferase domain (Domain)
 [649-947]  2.0000139277205e-124 SM00827
SM00827   PKS_AT
IPR020806 Polyketide synthase, phosphopantetheine-binding domain (Domain)
 [28-99]  2.70000183580794e-16 SM00823 [1784-1856]  1.60000240695997e-32 SM00823
SM00823   PKS_PP
IPR020807 Polyketide synthase, dehydratase domain (Domain)
 [1015-1177]  2.39999798157263e-82 SM00826
SM00826   PKS_DH
IPR020841 Polyketide synthase, beta-ketoacyl synthase domain (Domain)
 [119-543]  SM00825
SM00825   PKS_KS
IPR020842 Polyketide synthase/Fatty acid synthase, KR (Domain)
 [1497-1676]  1.60000240695997e-43 SM00822
SM00822   PKS_KR
SignalP No significant hit
TMHMM No significant hit
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