Characterization of the lnmKLM genes unveiling key intermediates for β-alkylation in leinamycin biosynthesis.

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.