Balhi_00110 Balhi_00110   Balhi_00130 Balhi_00130

Balhi_00120 : CDS information

close this sectionLocation

Organism
StrainDSM 5908
Entry nameBalhimycin
Contig
Start / Stop / Direction36,007 / 37,203 / + [in whole cluster]
36,007 / 37,203 / + [in contig]
Location36007..37203 [in whole cluster]
36007..37203 [in contig]
TypeCDS
Length1,197 bp (398 aa)
Click on the icon to see Genetic map.

close this sectionAnnotation

Category3.3 modification reduction
Productcytochrome P450
Product (GenBank)P450 monooxygenase
Gene
Gene (GenBank)oxyB
EC number
Keyword
  • 1st cross-linking
  • C-O-D ring
Note
Note (GenBank)
Reference
ACC
PmId
[10390204] Identification and analysis of the balhimycin biosynthetic gene cluster and its use for manipulating glycopeptide biosynthesis in Amycolatopsis mediterranei DSM5908. (Antimicrob Agents Chemother. , 1999)
[12404385] The Biosynthesis of Vancomycin-Type Glycopeptide Antibiotics-The Order of the Cyclization Steps This work was supported by the Deutsche Forschungsgemeinschaft (SFB 323) and by a grant of the EU (MEGATOP, QLK3-1999-00650). R. D. S. gratefully acknowledges the support of a Feodor-Lynen Fellowship granted by the Alexander-von-Humboldt Stiftung. We thank Corina Bihlmaier and Volker Pfeifer for help with transformation and Southern hybridization, J. A. Moss (La Jolla (USA)) for critical comments on the manuscript and Prof. Dr. M. E. Maier and Prof. Dr. H.-P. Fiedler (Tubingen) for generous support. (Angew Chem Int Ed Engl. , 2001)
[15651041] The biosynthesis of vancomycin-type glycopeptide antibiotics--a model for oxidative side-chain cross-linking by oxygenases coupled to the action of peptide synthetases. (Chembiochem. , 2005)
[16730832] Genetic analysis of the balhimycin (vancomycin-type) oxygenase genes. (J Biotechnol. , 2006)
[20337711] Genome mining in Amycolatopsis balhimycina for ferredoxins capable of supporting cytochrome P450 enzymes involved in glycopeptide antibiotic biosynthesis. (FEMS Microbiol Lett. , 2010)
comment
[PMID: 10390204](1999)
Amycolatopsis mediterranei DSM5908からグリコペプチド系抗生物質balhimycinの生合成に関する9,882bpのDNA断片を同定。そこにoxyA-bgtfCまで7つのcomplete genesを同定した。

oxyA-Cの推定産物はcytochrome P450 monooxygenasesへの有意な配列類似を示す。

putative oxygenase gene(oxyA_C末-oxyB_N末)の不活化株SP1-1は抗菌的に活性のある化合物を合成できなかった。

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[PMID: 12404385](2001)
oxyAと同様にoxyB, oxyCのmutantを作製し、その産物の構造から各oxygenaseの役割と順番を割り当てている。

1) OxyBによるC-O-D ring systemの形成
2) OxyAによるD-O-E ring systemの形成
3) OxyCによるbiaryl AB systemの形成

また、bicyclic C-O-D-O-E ring中間体は、1LeuのN-methylationと、4HpgのO-glycosylationの基質となれることもわかった。

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[PMID: 15651041](2005)
dpgA mutantではbicyclic hexapeptide、bpsC mutantではmonocyclic hexapeptideの蓄積があることから、OxyBによるCD ring形成はBpsB_module 6からBpsC_module 7へのhexapeptideの移動中かその少し前に起こるはずだと述べている。bpsC mutantでbicyclic hexapeptideが検出されないのは、BpsCでのdeletionのせいでOxyAとNRPS複合体の間の相互作用に必須な部位がないからであると説明されうる。

また、dpgA mutantにおいて、7つめのAAとしてDpgの代わりにL-4-hydroxyphenylglycine(Hpg)を含むtricyclic heptapeptideが得られたことから、BpsCとoxygenasesはいくらかの基質寛容性を示す。

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[PMID: 16730832](2006)
oxyA, oxyB, oxyCの非極性mutantsを作製し、閉環反応の順番を再確認している。
また、これらmutant株をvancomycin産生菌A. orientalis DSM40040由来の対応するoxygenase genesで補完すると、balhimycin産生は回復した。

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[PMID: 20337711](2010)
cytochrome P450の反応で電子供給するferredoxin partnersの捜索。

balhimycin産生株A. balhimycinaのドラフトゲノム配列から候補を見つけ、balFd-V と balFd-VII がA. balhimycina由来OxyB、vancomycin産生株A. orientalis由来CYP165Bに電子を供給してin vitroでの代謝回転を支持することを示している。

close this sectionSequence

selected fasta
>cytochrome P450 [P450 monooxygenase]
MNDDDPRPLHIRRQGLDPADELLAAGSLTRVTIGSGADAETHWMATAHALVRQVMGDHQR
FSTRRRWDPRDEIGGTGTFRPRELVGNLMDYDPPEHTRLRQKLTPGFTLRKMQRLQPYIE
QIVNERLDEMARAGSPADLVAFVADKVPGAVLCELIGVPRDDRATFMQLCHAHLDASRSQ
KRRAAAGEAFSRYLLAMIARERKDPGEGLIGAVVAEYGDEATDEELRGFCVQVMLAGDDN
ISGMIGLGVLALLRHPEQIDALRGGEQPAQRAVDELIRYLTVPYGPTPRIAKQDVTVGDQ
VIKAGESVICSLPAANRDPALVPDADRLDVTRDPVPHVAFGHGIHHCLGAALARLELRTV
FTALWRRFPDLRLADPAQETKFRLTTPAYGLTELMVAW
selected fasta
>cytochrome P450 [P450 monooxygenase]
TTGAATGATGACGACCCGCGGCCGCTGCACATTCGCCGGCAGGGCCTGGACCCGGCGGAC
GAGCTGCTCGCCGCCGGATCGCTGACGAGGGTCACCATCGGATCCGGAGCGGATGCCGAG
ACCCATTGGATGGCCACCGCGCACGCCCTCGTCCGGCAGGTGATGGGCGACCACCAGCGG
TTCAGCACCCGGCGCCGCTGGGACCCGCGGGACGAGATCGGCGGGACGGGCACCTTCCGG
CCGCGTGAACTGGTCGGCAACCTGATGGACTACGACCCGCCCGAGCACACGCGGCTGCGC
CAGAAGCTGACCCCCGGGTTCACGCTGCGCAAGATGCAGCGGCTGCAGCCGTACATCGAA
CAGATCGTCAACGAGCGACTCGACGAGATGGCGCGGGCGGGATCGCCCGCGGATCTGGTC
GCGTTCGTCGCCGACAAGGTGCCCGGCGCCGTGCTGTGCGAGCTGATCGGCGTGCCGAGG
GACGACCGGGCCACGTTCATGCAGCTGTGCCACGCGCATCTCGACGCCTCGCGAAGCCAG
AAACGGCGGGCGGCGGCGGGAGAGGCGTTCTCCCGCTACCTGCTGGCGATGATCGCCAGG
GAACGCAAGGACCCGGGCGAGGGGCTCATCGGAGCGGTCGTCGCCGAATACGGCGACGAA
GCCACGGACGAGGAGCTGCGCGGCTTCTGCGTGCAGGTGATGCTGGCTGGCGACGACAAC
ATCTCCGGCATGATCGGGCTCGGCGTGCTGGCGCTGCTGCGGCACCCCGAGCAGATCGAC
GCGTTGCGCGGCGGCGAACAGCCGGCGCAACGAGCCGTCGACGAGCTGATCCGGTACCTG
ACCGTGCCCTACGGCCCGACACCCCGCATCGCGAAGCAGGACGTCACCGTCGGGGACCAG
GTGATCAAGGCGGGCGAGAGCGTCATCTGCTCGCTCCCGGCGGCCAACCGCGACCCCGCC
CTCGTGCCGGACGCGGACCGGCTCGATGTCACGCGCGACCCCGTCCCGCACGTCGCGTTC
GGGCACGGGATCCACCACTGCCTGGGAGCCGCACTGGCCCGCCTCGAACTGCGCACGGTC
TTCACCGCGCTGTGGCGGCGGTTTCCCGACCTGCGGCTCGCGGATCCCGCCCAGGAGACC
AAGTTCCGCCTCACCACCCCCGCTTACGGGCTGACCGAGCTGATGGTCGCCTGGTGA

close this sectionFeature

BLASTP
Database:UniProtKB:2011_09 		show BLAST table
InterPro
Database:interpro:38.0
IPR001128 Cytochrome P450 (Family)
[5-398] 4.20003460493095e-89 SSF48264
SSF48264   Cytochrome_P450
[270-368] 1.3e-13 PF00067
PF00067   p450
[26-398] 6.90000000000007e-93 G3DSA:1.10.630.10
G3DSA:1.10.630.10   Cyt_P450
IPR002397 Cytochrome P450, B-class (Family)
[91-102] 1.20000117458134e-52 PR00359 [138-154] 1.20000117458134e-52 PR00359 [155-170] 1.20000117458134e-52 PR00359 [192-214] 1.20000117458134e-52 PR00359 [271-282] 1.20000117458134e-52 PR00359 [289-316] 1.20000117458134e-52 PR00359 [317-332] 1.20000117458134e-52 PR00359 [338-347] 1.20000117458134e-52 PR00359 [347-358] 1.20000117458134e-52 PR00359
PR00359   BP450
IPR017972 Cytochrome P450, conserved site (Conserved_site)
[340-349] PS00086
PS00086   CYTOCHROME_P450
SignalP No significant hit
TMHMM No significant hit
Balhi_00110 Balhi_00110   Balhi_00130 Balhi_00130
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