Work

Characterization of the lnmKLM Genes Unveiling Key Intermediates for β-Alkylation in Leinamycin Biosynthesis

Year: 2010

Type: article

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.

Source: Organic Letters

DOI: 10.1021/ol102838y

Authors: Yong Huang, Sheng-Xiong Huang, Jianhua Ju, Gongli Tang, Tao Liu, Ben Shen

Institutions: University of Wisconsin System, University of Wisconsin–Madison

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology (medical)

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funder: National Cancer Institute

Awards: G141094016, UWCCC National Cooperative Drug Discovery Group for Can*, G2271657281, AT-less Type I Polyketide Synthases