The Sequence of the Enterococcal Cytolysin Imparts Unusual

The enterococcal cytolysin is a two-component lantibiotic of unknown structure with hemolytic activity that is important for virulence. We prepared cytolysin by co-expression of each precursor peptide with the synthetase CylM in E. coli, and characterized its structure. Surprisingly, cytolysin is the first example of a lantibiotic containing lanthionine and methyllanthionine structures with different stereochemistries in the same peptide, which is determined by the sequence of the substrate peptide. The enterococcal cytolysin is a two-component lantibiotic made up of the posttranslationally modified peptides CylLL ″ and CylLS″. It is produced by many clinical isolates of Enterococcus faecalis and is toxic to a broad range of gram positive bacteria1–3. The enterococcal cytolysin is a unique lantibiotic in that it has hemolytic activity against eukaryotic cells in addition to its antimicrobial activity2,4. The production of cytolysin enhances virulence in infection models and its association with acute patient mortality is supported by epidemiological data5–7. Despite the intensive research focused on the biological functions and biosynthesis of the enterococcal cytolysin8–10, its structure ha