Radical <i>S</i>-Adenosylmethionine Sulfurtransferase MybB Catalyzed Formation of the 4-Thiazolidinone Core in Mycobacidin Represents an Intersection between Primary and Secondary Metabolism.

ABSTRACT: Mycobacidin is an antitubercular antibiotic structurally composed of a sulfur-containing 4-thiazolidinone ring, yet its biosynthesis including the mechanism of sulfur incorporation has remained an open question since its discovery in 1952. In this study, the mycobacidin biosynthetic gene cluster is identified from soil-dwelling Streptomyces, and the corresponding biosynthetic pathway starting with 7-oxoheptanoate is characterized. The radical SAM enzyme MybB catalyzes two sulfur insertion reactions, thereby bridging C₇ and C₁₀ to complete the 4-thiazolidinone heterocycle as the final step in mycobacidin maturation. MybB is a homologue of biotin synthase, and in both biosynthetic pathways, the bridging sulfur originates from the degradation of an enzymatic auxil

SUBMITTER: Zhao H 

PROVIDER: S-EPMC11826332 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature