Investigating the Function of Cryptic Cytochalasan Cytochrome P450 Monooxygenases Using Combinatorial Biosynthesis
2019; American Chemical Society; Volume: 21; Issue: 21 Linguagem: Inglês
10.1021/acs.orglett.9b03372
ISSN1523-7060
AutoresChongqing Wang, Kevin Becker, Sebastian Pfütze, Eric Kuhnert, Marc Stadler, Russell J. Cox, Elizabeth Skellam,
Tópico(s)Microbial Metabolic Engineering and Bioproduction
ResumoTailoring 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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