Cytochrome P450-mediated hydroxylation is required for polyketide macrolactonization in stambomycin biosynthesis - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Accéder directement au contenu
Article Dans Une Revue Journal of Antibiotics Année : 2014

Cytochrome P450-mediated hydroxylation is required for polyketide macrolactonization in stambomycin biosynthesis

Résumé

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.

Dates et versions

hal-01474997 , version 1 (23-02-2017)

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Citer

Lijiang Song, Luisa Laureti, Christophe Corre, Pierre Leblond, Bertrand Aigle, et al.. Cytochrome P450-mediated hydroxylation is required for polyketide macrolactonization in stambomycin biosynthesis. Journal of Antibiotics, 2014, 67 (1), pp.71 - 76. ⟨10.1038/ja.2013.119⟩. ⟨hal-01474997⟩
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