Accurate Substrate-Like Probes for Trapping Late-Stage Intermediates in Nonribosomal Peptide Synthetase Condensation Domains.

ABSTRACT: Nonribosomal peptide synthetases (NRPSs) are a family of multidomain enzymes dedicated to the production of peptide natural products. Central to NRPS function are condensation (C) domains, which catalyze peptide bond formation and a number of specialized transformations including dehydroamino acid and β-lactam synthesis. Structures of C domains in catalytically informative states are limited due to a lack of clear strategies for stabilizing C domain interactions with their substrates and client domains. Inspired by a β-lactam forming C domain, we report herein the synthesis and application of 1, which forms irreversible cross-links with engineered thiol nucleophiles in a C domain active site. Deployment of 1 demonstrates the synthetic tractability of trapping late-stage nasce

SUBMITTER: Wheadon MJ 

PROVIDER: S-EPMC10029145 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature