Blasticidin S Biosynthesis Involves a Unique Interplay between a Radical SAM Dehydratase, a Transaminase and an ATP-Grasp Ligase in Order to Avoid a Futile Cycle.

ABSTRACT: Blasticidin S is a peptidyl nucleoside that blocks protein synthesis in prokaryotes and eukaryotes. It is widely used in molecular biology as a selection agent. Despite its utility, the biosynthetic origin of its 2',3'-unsaturated-4'-aminoacyl-4'-deoxyhexopyranose core is only partially understood. Previously, the radical S-adenosylmethionine enzyme BlsE was shown to catalyze dehydration of cytosylglucuronic acid. Herein, this product is shown to be accepted by the pyridoxal phosphate-dependent enzyme BlsH catalyzing an α,β-dehydration coupled to amination affording cytosinine, the sugar core of blasticidin S. The ATP-grasp ligase BlsI is identified as the next enzyme catalyzing amide bond formation between cytosinine and β-arginine to yield demethylblasticidin

SUBMITTER: Lee YH 

PROVIDER: S-EPMC12352542 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature