Epoth_00060 Epoth_00060   Epoth_00080 Epoth_00080

Epoth_00070 : CDS information

close this sectionLocation

Organism
StrainSo ce90
Entry nameEpothilone
Contig
Start / Stop / Direction11,872 / 16,104 / + [in whole cluster]
11,872 / 16,104 / + [in contig]
Location11872..16104 [in whole cluster]
11872..16104 [in contig]
TypeCDS
Length4,233 bp (1,410 aa)
Click on the icon to see Genetic map.

close this sectionAnnotation

Category1.2 NRPS
Productnon-ribosomal peptide synthetase
Product (GenBank)nonribosomal peptide synthetase
Gene
Gene (GenBank)epoP
EC number
Keyword
  • cysteine
Note
Note (GenBank)
  • EPOS P; contains condensation/heterocyclization, cysteine adenylation, putative NAD(P)H oxidase, and peptidyl carrier domains
Reference
ACC
PmId
[10662695] The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium cellulosum So ce90. (Chem Biol. , 2000)
[11217802] Studies on the biosynthesis of epothilones: the biosynthetic origin of the carbon skeleton. (J Antibiot (Tokyo). , 2000)
comment
[PMID: 10662695](2000)
生合成cluster報告論文。
EPOS P: NRPS(HC, Acys, OX, PCP)

HC: modified condensation (heterocyclization) domain
Acys: adenylation domain specific for cysteine
OX: oxidase

EPOS Pは、EPOS Aによって供給されるacetyl-S-ACPとPCP-bound cysteineとの縮合や、分子内のcyclodehydrationによる初期thiazoline環の形成などに関与しているようだ。
NAD(P)H oxidase/reductaseに相同性があるがNRPSの配列では前例がないOX domainが、初期2-methylthiazoline→2-methythiazoleへの酸化に関与しているかもしれない。

--
[PMID:11217802](2000)
取り込み実験によりepothilone骨格の由来を調査。
epothilone生合成はacetateとcysteineに由来するthiazole部分の形成でスタートする。
Related Reference
ACC
Q9KIZ9
PmId
[10649995] Cloning and heterologous expression of the epothilone gene cluster. (Science. , 2000)
[10831849] Isolation and characterization of the epothilone biosynthetic gene cluster from Sorangium cellulosum. (Gene. , 2000)
[11564558] Epothilone biosynthesis: assembly of the methylthiazolylcarboxy starter unit on the EpoB subunit. (Chem Biol. , 2001)
[12911314] Oxidase domains in epothilone and bleomycin biosynthesis: thiazoline to thiazole oxidation during chain elongation. (Biochemistry. , 2003)
comment
2nd(Q9KIZ9) 97%, 0.0
Sorangium cellulosum (Polyangium cellulosum)_epoB
EpoB

Strain SMP44
Streptomyces coelicolorでepothilone biosynthetic gene clusterを発現してepothilone A and B産生を確認。

NRPSをepoPでなく、PKSとの通しでepoBとしている。これによって以降もひとつずつずれていく。

--
[PMID:12911314](2003)
EpoBのoxidase domainについてさらなる調査をした報告。
thiazoline → thiazole へのoxidase活性が実証されている。
Kinetic parameters測定あり。

close this sectionPKS/NRPS Module

1
C71..364
A550..953
OX1058..1223
PCP1317..1384

close this sectionSequence

selected fasta
>non-ribosomal peptide synthetase [nonribosomal peptide synthetase]
MTINQLLNELEHQGIKLAADGERLQIQAPKNALNPNLLARISEHKSTILTMLRQRLPAES
IVPAPAERHAPFPLTDIQESYWLGRTGAFTVPSGIHAYREYDCTDLDVPRLSRAFRKVVA
RHDMLRAHTLPDMMQVIEPKVDADIEIIDLRGLDRSTREARLVSLRDAMSHRIYDTERPP
LYHVVAVRLDERQTRLVLSIDLINVDLGSLSIIFKDWLSFYEDPETSLPVLELSYRDYVL
ALESRKKSEAHQRSMDYWKRRIAELPPPPTLPMKADPSTLKEIRFRHTEQWLPSDSWGRL
KRRVGERGLTPTGVILAAFSEVIGRWSASPRFTLNITLFNRLPVHPRVNDITGDFTSMVL
LDIDTTRDKSFEQRAKRIQEQLWEAMDHCDVSGIEVQREAARVLGIQRGALFPVVLTSAL
NQQVVGVTSLQRLGTPVYTSTQTPQLLLDHQLYEHDGDLVLAWDIVDGVFPPDLLDDMLE
AYVVFLRRLTEEPWGEQVRCSLPPAQLEARASANATNALLSEHTLHGLFAARVEQLPMQL
AVVSARKTLTYEELSRRSRRLGARLREQGARPNTLVAVVMEKGWEQVVAVLAVLESGAAY
VPIDADLPAERIHYLLDHGEVKLVLTQPWLDGKLSWPPGIQRLLVSEAGVEGDGDQPPMM
PIQTPSDLAYVIYTSGSTGLPKGVMIDHRGAVNTILDINERFEIGPGDRVLALSSLSFDL
SVYDVFGILAAGGTIVVPDASKLRDPAHWAELIEREKVTVWNSVPALMRMLVEHFEGRPD
SLARSLRLSLLSGDWIPVGLPGELQAIRPGVSVISLGGATEASIWSIGYPVRNVDLSWAS
IPYGRPLRNQTFHVLDEALEPRPVWVPGQLYIGGVGLALGYWRDEEKTRKSFLVHPETGE
RLYKTGDLGRYLPDGNIEFMGREDNQIKLRGYRVELGEIEETLKSHPNVRDAVIVPVGND
AANKLLLAYVVPEGTRRRAAEQDASLKTERIDARAHAAEADGLSDGERVQFKLARHGLRR
DLDGKPVVDLTGQDPREAGLDVYARRRSVRTFLEAPIPFVEFGRFLSCLSSVEPDGATLP
KFRYPSAGSTYPVQTYAYVKSGRIEGVDEGFYYYHPFEHRLLKLSDHGIERGAHVRQNFD
VFDEAAFNLLFVGRIDAIESLYGSSSREFCLLEAGYMAQLLMEQAPSCNIGVCPVGQFNF
EQVRPVLDLRHSDVYVHGMLGGRVDPRQFQVCTLGQDSSPRRATTRGAPPGREQHFADML
RDFLRTKLPEYMVPTVFVELDALPLTSNGKVDRKALRERKDTSSPRHSGHTAPRDALEEI
LVAVVREVLGLEVVGLQQSFVDLGATSIHIVRMRSLLQKRLDREIAITELFQYPNLGSLA
SGLRRDSRDLDQRPNMQDRVEVRRKGRRRS
selected fasta
>non-ribosomal peptide synthetase [nonribosomal peptide synthetase]
ATGACGATCAATCAGCTTCTGAACGAGCTCGAGCACCAGGGTATCAAGCTGGCGGCCGAT
GGGGAGCGCCTCCAGATACAGGCCCCCAAGAACGCCCTGAACCCGAACCTGCTCGCTCGA
ATCTCCGAGCACAAAAGCACGATCCTGACGATGCTCCGTCAGAGACTCCCCGCAGAATCC
ATCGTGCCCGCCCCAGCCGAGCGGCACGCTCCGTTTCCTCTCACAGACATCCAAGAATCC
TACTGGCTGGGCCGGACAGGAGCGTTTACGGTCCCCAGCGGGATCCACGCCTATCGCGAA
TACGACTGTACGGATCTCGACGTGCCGAGGCTGAGCCGCGCCTTTCGGAAAGTCGTCGCG
CGGCACGACATGCTTCGGGCCCACACGCTGCCCGACATGATGCAGGTGATCGAGCCTAAA
GTCGACGCCGACATCGAGATCATCGATCTGCGCGGGCTCGACCGGAGCACACGGGAAGCG
AGGCTCGTGTCGTTGCGAGATGCGATGTCGCACCGCATCTATGACACCGAGCGCCCTCCG
CTCTATCACGTCGTCGCCGTTCGGCTGGACGAGCGGCAAACCCGTCTCGTGCTCAGTATC
GATCTCATTAACGTTGACCTAGGCAGCCTGTCCATCATCTTCAAGGACTGGCTCAGCTTC
TACGAAGATCCCGAGACCTCTCTCCCTGTCCTGGAGCTCTCGTACCGCGATTATGTACTC
GCGCTGGAGTCTCGCAAGAAGTCTGAGGCGCATCAACGATCGATGGATTACTGGAAGCGG
CGCATCGCCGAGCTCCCACCTCCGCCGACGCTTCCGATGAAGGCCGATCCATCTACCCTG
AAGGAGATCCGCTTCCGGCACACGGAGCAATGGCTGCCGTCGGACTCCTGGGGTCGATTG
AAGCGGCGTGTCGGGGAGCGCGGGCTGACCCCGACGGGCGTCATCCTGGCTGCATTTTCC
GAGGTGATCGGGCGCTGGAGCGCGAGCCCCCGGTTTACGCTCAACATAACGCTCTTCAAC
CGGCTCCCCGTCCATCCGCGCGTGAACGATATCACCGGGGACTTCACGTCGATGGTCCTC
CTGGACATCGACACCACTCGCGACAAGAGCTTCGAACAGCGCGCTAAGCGTATTCAAGAG
CAGCTGTGGGAAGCGATGGATCACTGCGACGTAAGCGGTATCGAGGTCCAGCGAGAGGCC
GCCCGGGTCCTGGGGATCCAACGAGGCGCATTGTTCCCCGTGGTGCTCACGAGCGCGCTT
AACCAGCAAGTCGTTGGTGTCACCTCGTTGCAGAGGCTCGGAACTCCGGTGTACACCAGC
ACGCAGACTCCTCAGCTGCTGCTGGATCATCAGCTCTACGAGCACGATGGGGACCTCGTC
CTCGCGTGGGACATCGTCGACGGAGTGTTCCCGCCCGACCTTCTGGACGACATGCTCGAA
GCGTACGTCGTTTTTCTCCGGCGGCTCACTGAGGAACCATGGGGTGAACAGGTGCGCTGT
TCGCTTCCGCCTGCCCAGCTAGAAGCGCGGGCGAGCGCAAACGCGACCAACGCGCTGCTG
AGCGAGCATACGCTGCACGGCCTGTTCGCGGCGCGGGTCGAGCAGCTGCCCATGCAGCTC
GCCGTGGTGTCGGCGCGCAAGACGCTCACGTACGAAGAGCTTTCGCGCCGTTCGCGGCGA
CTTGGCGCGCGGCTGCGCGAGCAGGGGGCACGCCCGAACACATTGGTCGCGGTGGTGATG
GAGAAAGGCTGGGAGCAGGTTGTCGCGGTTCTCGCGGTGCTCGAGTCAGGCGCGGCCTAC
GTGCCGATCGATGCCGACCTACCGGCGGAGCGTATCCACTACCTCCTCGATCATGGTGAG
GTAAAGCTCGTGCTGACGCAGCCATGGCTGGATGGCAAACTGTCATGGCCGCCGGGGATC
CAGCGGCTGCTCGTGAGCGAGGCCGGCGTCGAAGGCGACGGCGACCAGCCTCCGATGATG
CCCATTCAGACACCTTCGGATCTCGCGTATGTCATCTACACCTCGGGATCCACAGGGTTG
CCCAAGGGGGTGATGATCGATCATCGGGGTGCCGTCAACACCATCCTGGACATCAACGAG
CGCTTCGAAATAGGGCCCGGAGACAGGGTGCTGGCGCTCTCCTCGCTGAGCTTCGATCTC
TCGGTCTATGATGTGTTCGGGATCCTGGCGGCGGGCGGTACGATCGTGGTGCCGGACGCG
TCCAAGCTGCGCGATCCGGCGCATTGGGCAGAGTTGATCGAACGAGAGAAGGTGACGGTG
TGGAACTCGGTGCCGGCGCTGATGCGGATGCTCGTCGAGCATTTTGAGGGTCGCCCCGAT
TCGCTCGCTAGGTCTCTGCGGCTTTCGCTGCTGAGCGGCGACTGGATCCCGGTGGGCCTG
CCTGGCGAGCTCCAGGCCATCAGGCCCGGCGTGTCGGTGATCAGCCTGGGCGGGGCCACC
GAAGCGTCGATCTGGTCCATCGGGTACCCCGTGAGGAACGTCGACCTATCGTGGGCGAGC
ATCCCCTACGGCCGTCCGCTGCGCAACCAGACGTTCCACGTGCTCGATGAGGCGCTCGAA
CCGCGCCCGGTCTGGGTTCCGGGGCAACTCTACATTGGCGGGGTCGGGCTGGCACTGGGC
TACTGGCGCGATGAAGAGAAGACGCGCAAGAGCTTCCTCGTGCACCCCGAGACCGGGGAG
CGCCTCTACAAGACCGGCGATCTGGGCCGCTACCTGCCCGATGGAAACATCGAGTTCATG
GGGCGTGAGGACAACCAAATCAAGCTTCGCGGATACCGCGTTGAGCTCGGGGAAATCGAG
GAAACGCTCAAGTCGCATCCGAACGTACGCGACGCGGTGATTGTGCCCGTCGGGAACGAC
GCGGCGAACAAGCTCCTTCTAGCCTATGTGGTCCCGGAGGGCACACGGAGACGCGCTGCC
GAGCAGGACGCGAGCCTCAAGACCGAGCGGATCGACGCGAGAGCACACGCCGCCGAAGCG
GACGGCTTGAGCGACGGCGAGAGGGTGCAGTTCAAGCTCGCTCGACACGGACTCCGGAGG
GACCTGGACGGAAAGCCCGTCGTCGATCTGACCGGGCAGGATCCGCGGGAGGCGGGGCTG
GACGTCTACGCGCGTCGCCGTAGCGTCCGAACGTTCCTTGAGGCCCCGATTCCGTTTGTT
GAGTTTGGTCGATTCCTGAGCTGCTTGAGCAGCGTGGAGCCCGACGGCGCGACCCTTCCC
AAATTCCGTTATCCATCGGCGGGCAGCACGTACCCGGTGCAAACCTACGCGTATGTCAAA
TCCGGCCGCATCGAGGGCGTGGACGAGGGCTTCTATTATTACCACCCGTTCGAGCACCGT
TTGCTGAAGCTCTCCGATCACGGGATCGAGCGCGGAGCGCACGTTCGGCAAAACTTCGAC
GTGTTCGATGAAGCGGCGTTCAACCTCCTGTTCGTGGGCAGGATCGACGCCATCGAGTCG
CTGTATGGATCGTCGTCGCGAGAATTTTGCCTGCTGGAGGCCGGATATATGGCGCAGCTC
CTGATGGAGCAGGCGCCTTCCTGCAACATCGGCGTCTGTCCGGTGGGGCAATTCAATTTT
GAACAGGTTCGGCCGGTTCTCGACCTGCGACATTCGGACGTTTACGTGCACGGCATGCTG
GGCGGGCGGGTAGACCCGCGGCAGTTCCAGGTCTGTACGCTCGGTCAGGATTCCTCACCG
AGGCGCGCCACGACGCGCGGCGCCCCTCCCGGCCGCGAGCAGCACTTCGCCGATATGCTT
CGCGACTTCTTGAGGACCAAACTACCCGAGTACATGGTGCCTACAGTCTTCGTGGAGCTC
GATGCGTTGCCGCTGACGTCCAACGGCAAGGTCGATCGTAAGGCCCTGCGCGAGCGGAAG
GATACCTCGTCGCCGCGGCATTCGGGGCACACGGCGCCACGGGACGCCTTGGAGGAGATC
CTCGTCGCGGTCGTACGGGAGGTGCTCGGGCTGGAGGTGGTCGGGCTCCAGCAGAGCTTC
GTCGATCTTGGTGCGACATCGATTCACATCGTTCGCATGAGGAGCCTGTTGCAGAAGAGG
CTGGATAGGGAGATCGCCATCACCGAGTTGTTCCAGTACCCGAACCTCGGCTCGCTGGCG
TCCGGTTTGCGCCGAGACTCGAGAGATCTAGATCAGCGGCCGAACATGCAGGACCGAGTG
GAGGTTCGGCGCAAGGGCAGGAGACGTAGCTAA
[1] C71..364
[1] A550..953
[1] OX1058..1223
[1] PCP1317..1384
[1] C211..1092
[1] A1648..2859
[1] OX3172..3669
[1] PCP3949..4152

close this sectionFeature

BLASTP
Database:UniProtKB:2011_09 		show BLAST table
InterPro
Database:interpro:38.0
IPR000415 Nitroreductase-like (Domain)
[1044-1210] 1.7e-15 PF00881
PF00881   Nitroreductase
[1041-1226] 1.1e-13 G3DSA:3.40.109.10
G3DSA:3.40.109.10   G3DSA:3.40.109.10
[1037-1242] 8.1000073432326e-18 SSF55469
SSF55469   Nitroreductase
IPR000873 AMP-dependent synthetase/ligase (Domain)
[550-953] 1e-111 PF00501
PF00501   AMP-binding
IPR001242 Condensation domain (Domain)
[71-364] 1.99999999999999e-42 PF00668
PF00668   Condensation
IPR009081 Acyl carrier protein-like (Domain)
[1310-1385] 1.29999924468179e-16 SSF47336
SSF47336   ACP_like
[1308-1385] 5.59999999999999e-19 G3DSA:1.10.1200.10
G3DSA:1.10.1200.10   ACP_like
[1321-1380] 1.3e-09 PF00550
PF00550   PP-binding
[1317-1384] PS50075
PS50075   ACP_DOMAIN
IPR010071 Amino acid adenylation domain (Domain)
[550-953] 1.39999999999997e-127 TIGR01733
TIGR01733   AA-adenyl-dom
IPR013624 Non-ribosomal peptide synthetase (Domain)
[388-445] 7.30000000000002e-14 PF08415
PF08415   NRPS
IPR020845 AMP-binding, conserved site (Conserved_site)
[671-682] PS00455
PS00455   AMP_BINDING
SignalP No significant hit
TMHMM No significant hit
Epoth_00060 Epoth_00060   Epoth_00080 Epoth_00080
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