Genome-Based Discovery of an Unprecedented Cyclization Mode in Fungal Sesterterpenoid Biosynthesis
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- 作者：Masahiro Okada ; Yudai Matsuda ; Takaaki Mitsuhashi ; Shotaro Hoshino ; Takahiro Mori ; Kazuya Nakagawa ; Zhiyang Quan ; Bin Qin ; Huiping Zhang ; Fumiaki Hayashi ; Hiroshi Kawaide ; Ikuro Abe
- 刊名：Journal of the American Chemical Society
- 出版年：2016
- 出版时间：August 10, 2016
- 年：2016
- 卷：138
- 期：31
- 页码：10011-10018
- 全文大小：466K
- 年卷期：0
- ISSN：1520-5126
文摘
Sesterterpenoids are a group of terpenoid natural products that are primarily biosynthesized via cyclization of the C25 linear substrate geranylfarnesyl pyrophosphate (GFPP). Although the long carbon chain of GFPP in theory allows for many different cyclization patterns, sesterterpenoids are relatively rare species among terpenoids, suggesting that many intriguing sesterterpenoid scaffolds have been overlooked. Meanwhile, the recent identification of the first sesterterpene synthase has allowed the discovery of new sesterterpenoids by the genome mining approach. In this study, we characterized the unusual fungal sesterterpene synthase EvQS and successfully obtained the sesterterpene quiannulatene (1) with a novel and unique highly congested carbon skeleton, which is further oxidized to quiannulatic acid (2) by the cytochrome P450 Qnn-P450. A mechanistic study of its cyclization from GFPP indicated that the biosynthesis employs an unprecedented cyclization mode, which involves three rounds of hydride shifts and two successive C–C bond migrations to construct the 5-6-5-5-5 fused ring system of 1.