title: Identification of a gene cluster of polyether antibiotic lasalocid from Streptomyces lasaliensis.
abstract: Elucidation of enzymatic polyether formation is a long-standing controversial issue in organic chemistry. To address this intriguing issue, identifying the actual substrate for epoxidation and sequential cyclization is essential. We selected the representative polyether ionophore, lasalocid, which has been proposed to undergo no modification at the late stage of biosynthesis. Cloning and a sequence analysis revealed seven polyketide synthase (PKS) genes, epoxidase and epoxide hydrolase genes for sequential ether formation, and several putative genes for supplying ethylmalonyl-CoA. Based on bioinformatic data, we propose the lasalocid biosynthetic pathway which involves characteristic aromatic ring formation and sequential cyclic ether formation. The finding of a thioesterase domain at the C-terminal of the seventh PKS indicates that intriguing oxidative cascade cyclization would occur after cleavage of the polyketide intermediate from PKS. Based on this observation, we have recently reported the enzymatic transformation of a bisepoxide intermediate to lasalocid with the recombinant epoxide hydrolase, Lsd19.
authors.affiliation: Division of Chemistry, Graduate School of Science, Hokkaido University.
authors.forename: Akira
authors.initials: A
authors.lastname: Migita
authors.forename: Mami
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirose
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Tokiwano
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Kinashi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Oikawa
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D003001:Cloning, Molecular; D003500:Cyclization; D004852:Epoxy Compounds; D007832:Lasalocid / Q000096:biosynthesis*; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D005810:Multigene Family; D048630:Polyketide Synthases / Q000235:genetics; D013302:Streptomyces / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D004852:Epoxy Compounds; D048630:Polyketide Synthases; D007832:Lasalocid