Molecular Basis for Asynchronous Chain Elongation During Rifamycin Antibiotic Biosynthesis.

ABSTRACT: The rifamycin synthetase (RIFS) from the bacterium Amycolatopsis mediterranei is a large (3.5 MDa) multienzyme system that catalyzes over 40 chemical reactions to generate a complex precursor to the antibiotic rifamycin B. It is considered a hybrid enzymatic assembly line and consists of an N-terminal nonribosomal peptide synthetase loading module followed by a decamodular polyketide synthase (PKS). While the biosynthetic functions are known for each enzymatic domain of RIFS, structural and biochemical analyses of this system from purified components are relatively scarce. Here, we examine the biosynthetic mechanism of RIFS through complementary crosslinking, kinetic, and structural analyses of its first PKS module (M1). Thiol-selective crosslinking of M1 provided a plausible molecu

SUBMITTER: Liu C 

PROVIDER: S-EPMC12236473 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature