Structure and Biosynthesis of Carnolysin, a Homologue of Enterococcal Cytolysin with d‑Amino Acids

• Published in: Journal of the American Chemical Society Vol. 136; no. 38; pp. 13150 - 13153
• Main Authors: Lohans, Christopher T, Li, Jessica L, Vederas, John C
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 24.09.2014
• Subjects: Alanine - analogs & derivatives; Alanine - chemical synthesis; Alanine - chemistry; Amino Acid Sequence; Amino Acids - chemical synthesis; Amino Acids - chemistry; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Antimicrobial Cationic Peptides - chemical synthesis; Antimicrobial Cationic Peptides - chemistry; Bacteriocins - chemical synthesis; Bacteriocins - chemistry; Carnobacteriaceae - chemistry; Enterococcus - chemistry; Methylation; Molecular Sequence Data; Perforin - chemical synthesis; Perforin - chemistry; Sulfides - chemical synthesis; Sulfides - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja5070813

Lantibiotics are a group of highly post-translationally modified bacterial antimicrobial peptides characterized by the presence of the thioether-containing amino acids lanthionine and methyllanthionine. Carnobacterium maltaromaticum C2 was found to produce a two-component lantibiotic homologous to enterococcal cytolysin. Through tandem mass spectrometry and NMR spectroscopy, the post-translational modifications of carnolysin were established, and the topologies of the lanthionine and methyllanthionine rings were determined. Chiral GC-MS analysis revealed that, like cytolysin, carnolysin contained lanthionine and methyllanthionine residues of unusual stereochemistry. Carnolysin, unlike cytolysin, was shown to contain d-alanine and unprecedented d-aminobutyrate derived from serine and threonine, respectively. Carnolysin was heterologously expressed in Escherichia coli, demonstrating that reductase CrnJ is involved in the formation of the d-amino acids.