title: Characterization of the lnmKLM genes unveiling key intermediates for β-alkylation in leinamycin biosynthesis.
abstract: Leinamycin (LNM, 1) biosynthesis is proposed to involve β-alkylation of the polyketide intermediate, catalyzed by LnmKLM. Inactivation of lnmK, lnmL, or lnmM afforded mutant strains that accumulated LNM K-1 (2), K-2 (3), K-3 (4), and isomers LNM K-1' (5), K-2' (6), and K-3' (7) whose polyketide origin was established by feeding experiments with sodium [1-(13)C]acetate. These findings confirm the indispensability of LnmKLM in 1 biosynthesis and suggest that β-alkylation proceeds on the growing polyketide intermediate while bound to the LNM polyketide synthase.
authors.affiliation: Division of Pharmaceutical Sciences, University of Wisconsin, Madison, Wisconsin 53705-2222, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Sheng-Xiong
authors.initials: SX
authors.lastname: Huang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ju
authors.forename: Gongli
authors.initials: G
authors.lastname: Tang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Ben
authors.initials: B
authors.lastname: Shen
mesh_terms: D000478:Alkylation; D007769:Lactams / Q000138:chemical synthesis*; D018942:Macrolides / Q000138:chemical synthesis*; D015394:Molecular Structure; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism*; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry / Q000235:genetics; D013844:Thiazoles / Q000138:chemical synthesis*; D013871:Thiones / Q000138:chemical synthesis*
chemical_list: D007769:Lactams; D018942:Macrolides; D013844:Thiazoles; D013871:Thiones; C059000:leinamycin; D048630:Polyketide Synthases