Radical-Mediated Nucleophilic Peptide Cross-Linking in Dynobactin Biosynthesis.

ABSTRACT: Dynobactins are recently discovered ribosomally synthesized and post-translationally modified peptide (RiPP) antibiotics that selectively kill Gram-negative pathogens by inhibiting the β-barrel assembly machinery (Bam) located on their outer membranes. Such activity of dynobactins derives from their unique cross-links between Trp1-Asn4 and His6-Tyr8. In particular, the His6-Tyr8 cross-link is formed between N_τ of His6 and C_β of Tyr8, an unprecedented type of cross-link in RiPP natural products. The mechanism of the C-N cross-link formation remains elusive. In this work, using in vitro characterizations, we demonstrate that both cross-links in dynobactins are biosynthesized by the radical S-adenosylmethionine (SAM) enzyme DynA. Subsequent mechanistic studies usi

SUBMITTER: Nguyen BX 

PROVIDER: S-EPMC11695099 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature