1. Genome-Based Discovery of an Unprecedented Cyclization Mode in Fungal Sesterterpenoid Biosynthesis
- Author
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Fumiaki Hayashi, Bin Qin, Takahiro Mori, Kazuya Nakagawa, Zhiyang Quan, Huiping Zhang, Masahiro Okada, Ikuro Abe, Takaaki Mitsuhashi, Hiroshi Kawaide, Yudai Matsuda, and Shotaro Hoshino
- Subjects
Sesterterpenes ,Stereochemistry ,Aspergillus oryzae ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Genome ,Catalysis ,Terpene ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Biosynthesis ,Geranylfarnesyl pyrophosphate ,Phylogeny ,Carbon chain ,Biological Products ,Alkyl and Aryl Transferases ,Emericella ,ATP synthase ,biology ,Terpenes ,010405 organic chemistry ,General Chemistry ,Carbon ,Recombinant Proteins ,Terpenoid ,0104 chemical sciences ,Diphosphates ,chemistry ,Cyclization ,biology.protein ,Genome, Fungal ,Hydrogen - Abstract
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.
- Published
- 2016