title: An unusual terpene cyclization mechanism involving a carbon-carbon bond rearrangement.
abstract: Terpene cyclization reactions are fascinating owing to the precise control of connectivity and stereochemistry during the catalytic process. Cyclooctat-9-en-7-ol synthase (CotB2) synthesizes an unusual 5-8-5 fused-ring structure with six chiral centers from the universal diterpene precursor, the achiral C20 geranylgeranyl diphosphate substrate. An unusual new mechanism for the exquisite CotB2-catalyzed cyclization that involves a carbon-carbon backbone rearrangement and three long-range hydride shifts is proposed, based on a powerful combination of in vivo studies using uniformly (13)C-labeled glucose and in vitro reactions of regiospecifically deuterium-substituted geranylgeranyl diphosphate substrates. This study shows that CotB2 elegantly demonstrates the synthetic virtuosity and stereochemical control that evolution has conferred on terpene synthases.
authors.affiliation: Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan).
authors.forename: Ayuko
authors.initials: A
authors.lastname: Meguro
authors.forename: Yudai
authors.initials: Y
authors.lastname: Motoyoshi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Teramoto
authors.forename: Shota
authors.initials: S
authors.lastname: Ueda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Totsuka
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ando
authors.forename: Takeo
authors.initials: T
authors.lastname: Tomita
authors.forename: Seung-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kimura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Igarashi
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sawa
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shinada
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishiyama
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kuzuyama
mesh_terms: D002244:Carbon / Q000737:chemistry*; D003500:Cyclization; D013729:Terpenes / Q000737:chemistry*
chemical_list: D013729:Terpenes; D002244:Carbon
keywords: biosynthesis; enzyme catalysis; reaction mechanism; terpenes