title: "Cation-Stitching Cascade": exquisite control of terpene cyclization in cyclooctatin biosynthesis.
abstract: Terpene cyclization is orchestrated by terpene cyclases, which are involved in the biosynthesis of various cyclic natural products, but understanding the origin and mechanism of the selectivity of terpene cyclization is challenging. In this work, we describe an in-depth mechanistic study on cyclooctatin biosynthesis by means of theoretical calculations combined with experimental methods. We show that the main framework of cyclooctatin is formed through domino-type carbocation transportation along the terpene chain, which we call a "cation-stitching cascade", including multiple hydrogen-shifts and a ring rearrangement that elegantly determine the stereoselectivity.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|Elements Chemistry Laboratory, RIKEN, and RIKEN Center for Sustainable Resource Science (Wako campus), 2-1 Hirosawa, Wako-shi, Saitama-ken 351-0198, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Sato
authors.affiliation: Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Teramoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|Elements Chemistry Laboratory, RIKEN, and RIKEN Center for Sustainable Resource Science (Wako campus), 2-1 Hirosawa, Wako-shi, Saitama-ken 351-0198, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Masumoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|Elements Chemistry Laboratory, RIKEN, and RIKEN Center for Sustainable Resource Science (Wako campus), 2-1 Hirosawa, Wako-shi, Saitama-ken 351-0198, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tezuka
authors.affiliation: Department of Material Science, Graduate School of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Material Science, Graduate School of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Department of Material Science, Graduate School of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Totsuka
authors.affiliation: Department of Material Science, Graduate School of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shinada
authors.affiliation: Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishiyama
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|Elements Chemistry Laboratory, RIKEN, and RIKEN Center for Sustainable Resource Science (Wako campus), 2-1 Hirosawa, Wako-shi, Saitama-ken 351-0198, Japan.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kuzuyama
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|Elements Chemistry Laboratory, RIKEN, and RIKEN Center for Sustainable Resource Science (Wako campus), 2-1 Hirosawa, Wako-shi, Saitama-ken 351-0198, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Uchiyama
mesh_terms: D002412:Cations / Q000737:chemistry; D003500:Cyclization; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism*; D007553:Isotope Labeling; D013237:Stereoisomerism; D013729:Terpenes / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D002412:Cations; D004224:Diterpenes; D013729:Terpenes; C078947:cyclooctatin