Efficient Biosynthesis of Fungal Polyketides Containing the Dioxabicyclo-octane Ring System
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- 作者：Xu-Ming Mao ; Zha-Jun Zhan ; Matthew N. Grayson ; Man-Cheng Tang ; Wei Xu ; Yong-Quan Li ; Wen-Bing Yin ; Hsiao-Ching Lin ; Yit-Heng Chooi ; K. N. Houk ; Yi Tang
- 刊名：Journal of the American Chemical Society
- 出版年：2015
- 出版时间：September 23, 2015
- 年：2015
- 卷：137
- 期：37
- 页码：11904-11907
- 全文大小：309K
- ISSN：1520-5126
文摘
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 伪-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.