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Genome mining in amycolatopsis balhimycina for ferredoxins capable of supporting cytochrome P450 enzymes involved in glycopeptide antibiotic biosynthesis


Geib, N; Weber, T; Wörtz, T; Zerbe, K; Wohlleben, W; Robinson, J A (2010). Genome mining in amycolatopsis balhimycina for ferredoxins capable of supporting cytochrome P450 enzymes involved in glycopeptide antibiotic biosynthesis. FEMS Microbiology Letters, 306(1):45-53.

Abstract

Ferredoxins are required to supply electrons to the cytochrome P450 enzymes involved in cross-linking reactions during the biosynthesis of the glycopeptide antibiotics balhimycin and vancomycin. However, the biosynthetic gene clusters for these antibiotics contain no ferredoxin- or ferredoxin reductase-like genes. In a search for potential ferredoxin partners for these P450s, we report here an in silico analysis of the draft genome sequence of the balhimycin producer Amycolatopsis balhimycina, which revealed 11 putative Fe-S-containing ferredoxin genes. We show that two members (balFd-V and balFd-VII), produced as native-like holo-[3Fe-4S] ferredoxins in E. coli, could supply electrons to the P450 OxyB (CYP165B) from both A. balhimycina and the vancomycin producer A. orientalis, and support in vitro turnover of peptidyl carrier protein-bound peptide substrates into monocyclic cross-linked products. These results show that ferredoxins encoded in the antibiotic-producing strain can act in a degenerate manner in supporting the catalytic functions of glycopeptide biosynthetic P450 enzymes from the same as well as heterologous gene clusters.

Abstract

Ferredoxins are required to supply electrons to the cytochrome P450 enzymes involved in cross-linking reactions during the biosynthesis of the glycopeptide antibiotics balhimycin and vancomycin. However, the biosynthetic gene clusters for these antibiotics contain no ferredoxin- or ferredoxin reductase-like genes. In a search for potential ferredoxin partners for these P450s, we report here an in silico analysis of the draft genome sequence of the balhimycin producer Amycolatopsis balhimycina, which revealed 11 putative Fe-S-containing ferredoxin genes. We show that two members (balFd-V and balFd-VII), produced as native-like holo-[3Fe-4S] ferredoxins in E. coli, could supply electrons to the P450 OxyB (CYP165B) from both A. balhimycina and the vancomycin producer A. orientalis, and support in vitro turnover of peptidyl carrier protein-bound peptide substrates into monocyclic cross-linked products. These results show that ferredoxins encoded in the antibiotic-producing strain can act in a degenerate manner in supporting the catalytic functions of glycopeptide biosynthetic P450 enzymes from the same as well as heterologous gene clusters.

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Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Date:2010
Deposited On:24 Jan 2011 14:24
Last Modified:07 Dec 2017 05:17
Publisher:Wiley-Blackwell
ISSN:0378-1097
Funders:SNF
Additional Information:The definitive version is available at www.blackwell-synergy.com.
Publisher DOI:https://doi.org/10.1111/j.1574-6968.2010.01933.x
PubMed ID:20337711

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