Controlling Substrate- and Stereospecificity of Condensation Domains in Nonribosomal Peptide Synthetases.

ABSTRACT: Nonribosomal peptide synthetases (NRPSs) are sophisticated molecular machines that biosynthesize peptide drugs. In attempts to generate new bioactive compounds, some parts of NRPSs have been successfully manipulated, but especially the influence of condensation (C-)domains on substrate specificity remains enigmatic and poorly controlled. To understand the influence of C-domains on substrate preference, we extensively evaluated the peptide formation of C-domain mutants in a bimodular NRPS system. Thus, we identified three key mutations that govern the preference for stereoconfiguration and side-chain identity. These mutations show similar effects in three different C-domains (GrsB1, TycB1, and SrfAC) when di- or pentapeptides are synthesized in vitro or in vivo. Strikingly, mu

SUBMITTER: Peng H 

PROVIDER: S-EPMC10949931 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature