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

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 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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Journal of Antibiotics, Nature Publishing Group: Open Access Hybrid Model Option B, 2014, 67 (1), pp.71 - 76. 〈10.1038/ja.2013.119〉
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https://hal.univ-lorraine.fr/hal-01474997
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Soumis le : jeudi 23 février 2017 - 13:38:29
Dernière modification le : vendredi 15 décembre 2017 - 09:22:02

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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, Nature Publishing Group: Open Access Hybrid Model Option B, 2014, 67 (1), pp.71 - 76. 〈10.1038/ja.2013.119〉. 〈hal-01474997〉

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