Efficient Biosynthesis of Fungal Polyketides Containing the Dioxabicyclo-octane Ring System

X.M. Mao, Z.J. Zhan, M.N. Grayson, M.C. Tang, W. Xu, Y.Q. Li, W.B. Yin, H.C. Lin, Heng Chooi, K.N. Houk, Y. Tang

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Abstract

© 2015 American Chemical Society. Aurovertins are fungal polyketides that exhibit potent inhibition of adenosine triphosphate synthase. Aurovertins contain a 2,6-dioxabicyclo[3.2.1]octane ring that is proposed to be derived from a polyene precursor through regioselective oxidations and epoxide openings. In this study, we identified only four enzymes required to produce aurovertin E. The core polyketide synthase produces a polyene α-pyrone. Following pyrone O-methylation by a methyltransferase, a flavin-dependent mono-oxygenase and an epoxide hydrolase can iteratively transform the terminal triene portion of the precursor into the dioxabicyclo[3.2.1]octane scaffold. We demonstrate that a tetrahydrofuranyl polyene is the first stable intermediate in the transformation, which can undergo epoxidation and anti-Baldwin 6-endo-tet ring opening to yield the cyclic ether product. Our results further demonstrate the highly concise and efficient ways in which fungal biosynthetic pathways can generate complex natural product scaffolds.
Original languageEnglish
Pages (from-to)11904-11907
JournalJournal of the American Chemical Society
Volume137
Issue number37
DOIs
Publication statusPublished - 2015

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Mao, X. M., Zhan, Z. J., Grayson, M. N., Tang, M. C., Xu, W., Li, Y. Q., ... Tang, Y. (2015). Efficient Biosynthesis of Fungal Polyketides Containing the Dioxabicyclo-octane Ring System. Journal of the American Chemical Society, 137(37), 11904-11907. https://doi.org/10.1021/jacs.5b07816