Structural Basis for Iterative Methylation by a Cobalamin-dependent Radical S-Adenosylmethionine Enzyme in Cystobactamids Biosynthesis.

ABSTRACT: Cystobactamids are non-ribosomal peptide natural products that function as DNA gyrase inhibitors, exhibiting significant antibacterial activity. They are isolated from Cystobacter sp. Cbv34 and contain various alkoxy groups on para-aminobenzoic acid moieties, which are believed to play a crucial role in antibacterial functions. The alkoxy groups are generated by iterative methylations on a methoxy group by the cobalamin (Cbl)-dependent radical S-adenosylmethionine (SAM) enzyme CysS. CysS catalyzes up to three methylations to give ethoxy, isopropoxy, sec-butoxy, and tert-butoxy groups. For each methylation, CysS uses a ping-pong mechanism in which two molecules of SAM are consumed. One SAM is used to methylate cob(I)alamin, while another generates a 5'-deoxyadenosyl 5'-radical to initiate s

SUBMITTER: Cui J 

PROVIDER: S-EPMC12667779 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature