Biosynthesis of peptide-nucleobase hybrids in ribosomal peptides.

ABSTRACT: The main biopolymers in nature are oligonucleotides and polypeptides. However, naturally occurring peptide-nucleobase hybrids are rare. Here we report the characterization of the founding member of a class of peptide-nucleobase hybrid natural products with a pyrimidone motif from a widely distributed ribosomally synthesized and post-translationally modified (RiPP) biosynthetic pathway. This pathway features two steps where a heteromeric RRE-YcaO-dehydrogenase complex catalyzes the formation of a six-membered pyrimidone ring from an asparagine residue on the precursor peptide, and an acyl esterase selectively recognizes this moiety to cleave the C-terminal follower peptide. Mechanistic studies reveal that the pyrimidone formation occurs in a substrate-assisted catalysis manner, requiring a

SUBMITTER: Pei ZF 

PROVIDER: S-EPMC11912545 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature