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Investigating the Function of Cryptic Cytochalasan Cytochrome P450 Monooxygenases Using Combinatorial Biosynthesis.
Wang, Chongqing ; Becker, Kevin ; Pfütze, Sebastian ; Kuhnert, Eric ; ; Cox, Russell J ; Skellam, Elizabeth
Wang, Chongqing
Becker, Kevin
Pfütze, Sebastian
Kuhnert, Eric
Cox, Russell J
Skellam, Elizabeth
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2019-10-23
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Abstract
Tailoring enzymes in cytochalasan biosynthesis are relatively promiscuous. Exploiting this property, we deduced the function of four cryptic cytochrome P450 monooxygenases via heterologous expression of six cytochrome P450-encoding genes, originating from Hypoxylon fragiforme and Pyricularia oryzae, in pyrichalasin H ΔP450 strains. Three cryptic cytochrome P450 enzymes (HffD, HffG, and CYP1) restored pyrichalasin H production in mutant strains, while CYP3 catalyzed a site-selective epoxidation leading to the isolation of three novel cytochalasans.
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Org Lett. 2019 Nov 1;21(21):8756-8760. doi: 10.1021/acs.orglett.9b03372.
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en
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1523-7052
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Attribution-NonCommercial-ShareAlike 4.0 International
