Radical SAM-dependent ether crosslink in daropeptide biosynthesis.

ABSTRACT: Darobactin is a ribosomally synthesized and post-translationally modified peptide (RiPP), which possesses potent activity against various Gram-negative bacteria. Darobactin features a highly unique bicyclic scaffold, consisting of an ether crosslink between two Trp residues and a C-C crosslink between a Lys and a Trp. Here we report in vivo and in vitro activity of darobactin synthase DarE. We show DarE is a radical S-adenosylmethionine (rSAM) enzyme and is solely responsible for forming the bicyclic scaffold of darobactin. DarE mainly produced the ether-crosslinked product in vitro, and when the assay was performed in H₂¹⁸O, apparent ¹⁸O incorporation was observed into the ether-crosslinked product. These observations suggested an rSAM-dependent process in

SUBMITTER: Guo S 

PROVIDER: S-EPMC9055067 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature