Ketosynthase Domain Catalyzes β-Lactonization in the Biosynthesis of the HMG-CoA Synthase Inhibitor Hymeglusin.

ABSTRACT: Hymeglusin (1) is a fungal polyketide consisting of a β-lactone ring with a unique (3R,4R) configuration. 1 is a potent 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase inhibitor. Because it circumvents drug resistance in methicillin-resistant Staphylococcus aureus (MRSA), combination therapy using 1 would be a promising strategy for the treatment of infectious diseases caused by MRSA. Despite its pharmaceutical importance, the biosynthesis of 1, with respect to the formation of the characteristic β-lactone ring that is essential for its activity, had not been elucidated to date. During our genome mining of fungal highly reducing polyketide synthases (HR-PKSs), we identified a biosynthetic gene cluster for 1 in Nigrospora fung

SUBMITTER: Hirokawa M 

PROVIDER: S-EPMC12291444 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature