Abstract
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 β-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.
Original language | English |
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Pages (from-to) | 71-76 |
Number of pages | 6 |
Journal | Journal of Antibiotics |
Volume | 67 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2014 |
Externally published | Yes |
Keywords
- Acyl carrier protein
- Cytochrome P450
- Hydroxylation
- Macrolactonization
- Polyketide synthase
- Streptomyces ambofaciens
- Thioesterase