期刊
JOURNAL OF ANTIBIOTICS
卷 67, 期 1, 页码 71-76出版社
JAPAN ANTIBIOTICS RESEARCH ASSOC
DOI: 10.1038/ja.2013.119
关键词
acyl carrier protein; cytochrome P450; hydroxylation; macrolactonization; polyketide synthase; Streptomyces ambofaciens; thioesterase
资金
- European Commission [FP6-5224]
- Advantage West Midlands
- European Regional Development Fund
Many polyketide antibiotics contain macrolactones that arise from polyketide synthase chain release via thioesterase (TE) domain-catalyzed macrolactonization. The hydroxyl groups utilized in such macrolactonization reactions typically derive from reduction of beta-ketothioester intermediates in polyketide chain assembly. The stambomycins are a group of novel macrolide antibiotics with promising anticancer activity that we recently discovered via rational activation of a silent polyketide biosynthetic gene cluster in Streptomyces ambofaciens. Here we report that the hydroxyl group utilized for formation of the macrolactone in the stambomycins is derived from cytochrome P450-catalyzed hydroxylation of the polyketide chain rather than keto reduction during chain assembly. This is a novel mechanism for macrolactone formation in polyketide antibiotic biosynthesis.
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