title: Biosynthesis of versipelostatin: identification of an enzyme-catalyzed [4+2]-cycloaddition required for macrocyclization of spirotetronate-containing polyketides.
abstract: Versipelostatin (VST) is an unusual 17-membered macrocyclic polyketide product that contains a spirotetronate skeleton. In this study, the entire VST biosynthetic gene cluster (vst) spanning 108 kb from Streptomyces versipellis 4083-SVS6 was identified by heterologous expression using a bacterial artificial chromosome vector. Here, we demonstrate that an enzyme, VstJ, catalyzes the stereoselective [4+2]-cycloaddition between the conjugated diene and the exocyclic olefin of a newly identified tetronate-containing intermediate to form the spirotetronate skeleton during VST biosynthesis.
authors.affiliation: Biotechnology Research Center, The University of Tokyo , 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Junko
authors.initials: J
authors.lastname: Hashimoto
authors.forename: Kuniko
authors.initials: K
authors.lastname: Teruya
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirano
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shin-ya
authors.forename: Haruo
authors.initials: H
authors.lastname: Ikeda
authors.forename: Hung-wen
authors.initials: HW
authors.lastname: Liu
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishiyama
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kuzuyama
mesh_terms: D055162:Biocatalysis; D061565:Cycloaddition Reaction; D018942:Macrolides; D005810:Multigene Family; D009844:Oligosaccharides / Q000096:biosynthesis*; D061065:Polyketides / Q000737:chemistry* / Q000378:metabolism*; D013141:Spiro Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D018942:Macrolides; D009844:Oligosaccharides; D061065:Polyketides; D013141:Spiro Compounds; C490154:versipelostatin