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

Journal of the American Chemical Society
Xu-Ming MaoYi Tang

Abstract

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.

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Citations

Feb 7, 2016·Fungal Genetics and Biology : FG & B·Carly BondLi Li
Dec 13, 2016·Chemical Reviews·Man-Cheng TangYi Tang
Aug 30, 2018·Angewandte Chemie·Christopher T Walsh, Bradley S Moore
Aug 26, 2016·Beilstein Journal of Organic Chemistry·Franziska Hemmerling, Frank Hahn
Oct 2, 2020·Natural Product Reports·Lena Barra, Ikuro Abe
Nov 4, 2017·Applied Microbiology and Biotechnology·Zihui MaWen-Bing Yin
Mar 13, 2019·Applied Microbiology and Biotechnology·Phuong Nguyen TranPao-Yang Chen
Apr 7, 2019·Proceedings of the National Academy of Sciences of the United States of America·Yasuko ArakiKiyoshi Kita
Jun 15, 2019·Natural Product Reports·Jia Jia ZhangBradley S Moore
Aug 12, 2020·Angewandte Chemie·Zhuan ZhangYi Tang
Apr 14, 2016·Angewandte Chemie·Tsuyoshi YamamotoKenji Watanabe
Jun 4, 2018·Applied Microbiology and Biotechnology·Wei LiWen-Bing Yin
Oct 28, 2020·Organic & Biomolecular Chemistry·James W MarshallThomas J Simpson
Sep 18, 2020·European Journal of Medicinal Chemistry·Bhargav A PatelBrian S J Blagg
Jan 1, 2021·Current Opinion in Biotechnology·Hui Tao, Ikuro Abe
Apr 17, 2019·Organic Letters·Cheng FengYi Zou
Dec 14, 2017·Biochemistry·Christopher T Walsh, Yi Tang

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