title: Cyclolavandulyl skeleton biosynthesis via both condensation and cyclization catalyzed by an unprecedented member of the cis-isoprenyl diphosphate synthase superfamily.
abstract: A cyclolavandulyl group is a C10 monoterpene with a branched and cyclized carbon skeleton. This monoterpene is rarely found in nature, and its biosynthesis is poorly understood. To determine the biosynthesis mechanism of this monoterpene, we sequenced the genome of Streptomyces sp. CL190, which produces lavanducyanin, a phenazine with an N-linked cyclolavandulyl structure. Sequencing and homology searches identified one candidate gene product that consists of only a cis-isoprenyl diphosphate synthase domain. Disruption of the gene and biochemical analysis of the recombinant enzyme demonstrated that the enzyme synthesized a cyclolavandulyl diphosphate essential for the biosynthesis of lavanducyanin. This enzyme is an unprecedented terpene synthase that catalyzes both the condensation of the C5 isoprene units and subsequent cyclization to form the cyclolavandulyl monoterpene structure.
authors.affiliation: Biotechnology Research Center, The University of Tokyo , 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Ozaki
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
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: D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002070:Butadienes / Q000737:chemistry / Q000378:metabolism*; D003500:Cyclization; D011756:Diphosphates / Q000737:chemistry / Q000378:metabolism*; D005798:Genes, Bacterial; D045782:Hemiterpenes / Q000737:chemistry / Q000378:metabolism*; D039821:Monoterpenes / Q000737:chemistry / Q000378:metabolism*; D010420:Pentanes / Q000737:chemistry / Q000378:metabolism*; D010619:Phenazines / Q000737:chemistry / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D002070:Butadienes; D011756:Diphosphates; D045782:Hemiterpenes; D039821:Monoterpenes; D010420:Pentanes; D010619:Phenazines; C005059:isoprene; C060460:lavanducyanin; D019883:Alkyl and Aryl Transferases; C108877:terpene synthase