title: Genome-Based Discovery of an Unprecedented Cyclization Mode in Fungal Sesterterpenoid Biosynthesis.
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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okada
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yudai
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Mitsuhashi
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Hoshino
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mori
authors.affiliation: Institute of Agriculture, Tokyo University of Agriculture and Technology , 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Quan
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Bin
authors.initials: B
authors.lastname: Qin
authors.affiliation: RIKEN Center for Life Science Technologies , 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhang
authors.affiliation: RIKEN Center for Life Science Technologies , 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Hayashi
authors.affiliation: Institute of Agriculture, Tokyo University of Agriculture and Technology , 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaide
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Ikuro
authors.initials: I
authors.lastname: Abe
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000737:chemistry; D001236:Aspergillus oryzae; D001688:Biological Products / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D011756:Diphosphates / Q000737:chemistry; D032842:Emericella; D016681:Genome, Fungal; D006859:Hydrogen / Q000737:chemistry; D010802:Phylogeny; D011994:Recombinant Proteins / Q000737:chemistry; D054830:Sesterterpenes / Q000096:biosynthesis*; D013729:Terpenes / Q000737:chemistry*
chemical_list: D001688:Biological Products; D011756:Diphosphates; D011994:Recombinant Proteins; D054830:Sesterterpenes; D013729:Terpenes; C107241:diphosphoric acid; D002244:Carbon; D006859:Hydrogen; D019883:Alkyl and Aryl Transferases