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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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https://hal.univ-lorraine.fr/hal-01474997
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Submitted on : Thursday, February 23, 2017 - 1:38:29 PM
Last modification on : Thursday, January 7, 2021 - 3:43:41 PM

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Lijiang Song, Luisa Laureti, Christophe Eric 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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