Song, Lijiang, Laureti, Luisa, Corre, Christophe, Leblond, Pierre, Aigle, Bertrand and Challis, Gregory L. (2014) Cytochrome P450-mediated hydroxylation is required for polyketide macrolactonization in stambomycin biosynthesis. The Journal of Antibiotics, Volume 67 (Number 1). pp. 71-76. doi:10.1038/ja.2013.119

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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.

Item Type:	Journal Article
Divisions:	Faculty of Science, Engineering and Medicine > Science > Chemistry
Journal or Publication Title:	The Journal of Antibiotics
Publisher:	Nature Publishing Group
ISSN:	0021-8820
Official Date:	January 2014
Dates:	Date Event January 2014 Published 13 November 2013 Available 17 October 2013 Accepted 22 July 2013 Submitted
Volume:	Volume 67
Number:	Number 1
Page Range:	pp. 71-76
DOI:	10.1038/ja.2013.119
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access

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