Enzyme-Primed Native Chemical Ligation Produces Autoinducing Cyclopeptides in Clostridia.

ABSTRACT: Clostridia coordinate many important processes such as toxin production, infection, and survival by density-dependent communication (quorum sensing) using autoinducing peptides (AIPs). Although clostridial AIPs have been proposed to be (thio)lactone-containing peptides, their true structures remain elusive. Here, we report the genome-guided discovery of an AIP that controls endospore formation in Ruminiclostridium cellulolyticum. Through a combination of chemical synthesis and chemical complementation assays with a mutant strain, we reveal that the genuine chemical mediator is a homodetic cyclopeptide (cAIP). Kinetic analyses indicate that the mature cAIP is produced via a cryptic thiolactone intermediate that undergoes a rapid S→N acyl shift, in a manner similar to intramolecular native c

SUBMITTER: Molloy EM 

PROVIDER: S-EPMC8251862 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature