title: Cyclization mechanism for the synthesis of macrocyclic antibiotic lankacidin in Streptomyces rochei.
abstract: The lankacidin biosynthetic gene cluster in Streptomyces rochei strain 7434AN4 was found to span 31 kb of the giant linear plasmid pSLA2-L and contain a polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) hybrid gene (lkcA), type I PKS genes, and pyrroloquinoline quinone (PQQ) biosynthetic genes (lkcK-lkcO). Feeding of PQQ to a pqq mutant restored the lankacidin production, suggesting its crucial role in an oxidation process. However, formation of the 17-membered macrocyclic ring was not catalyzed by PQQ-dependent dehydrogenase (Orf23), but was by flavin-dependent amine oxidase (LkcE). Compound LC-KA05 isolated from an lkcE disruptant was an acyclic intermediate lacking the C2-C18 linkage. These results suggested a cyclization mechanism for the synthesis of the lankacidin macrocyclic skeleton.
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8530, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Arakawa
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sugino
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kodama
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ishii
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Kinashi
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003360:Cosmids; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D005810:Multigene Family; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; C008250:lankacidins