Rearrangement of Thiodepsipeptides by S–N Acyl Shift Delivers Homodetic Autoinducing Peptides

Group behavior in many bacteria relies on chemically induced communication called quorum sensing (QS), which plays important roles in regulation of colonization, biofilm formation, and virulence. In Gram-positive bacteria, QS is often mediated by cyclic ribosomally synthesized and posttranslationally modified peptides (RiPPs). In staphylococci for example, most of these so-called autoinducing peptides (AIPs) contain a conserved thiolactone functionality, which has been predicted to constitute a structural feature of AIPs from other species as well. Here, we show that pentameric AIPs from Lactobacillus plantarum, Clostridium perfringens, and Listeria monocytogenes that were previously presumed to be thiolactone-containing structures readily rearrange to become homodetic cyclopeptides. This finding has implications for the developing understanding of the cross-species communication of bacteria and may help guide the discovery of peptide ligands to perturb their function.