lanthionine

Lanthionine is a non-proteinogenic amino acid motif that contains a sulfur-containing thioether linkage. In the natural products known as lantibiotics, lanthionine residues form crosslinks within ribosomally synthesized and post-translationally modified peptides, contributing to their rigidity and proteolytic resistance.

The crosslinks arise when serine or threonine residues are dehydrated to dehydroalanine or dehydrobutyrine, followed by a cysteine thiol adding across the double bond. This process yields lanthionine bridges (Lan) or methyllanthionine bridges (MeLan), depending on the residues involved and the specific modification pattern of the peptide.

Biosynthetically, lantibiotics are produced from precursor peptides encoded by dedicated gene clusters. Enzymes such as LanB (dehydratase) and LanC (cyclase) catalyze dehydration and cyclization; in some systems a multifunctional LanM enzyme carries out both steps. The mature lantibiotics contain one or more lanthionine or methyllanthionine rings that define their three-dimensional structure and activity.

Representative lantibiotics include nisin, epidermin, gallidermin, and subtilin. These compounds exhibit antimicrobial activity primarily against Gram-positive bacteria, in part by binding to lipid II and disrupting cell membranes. The lanthionine crosslinks are central to their mechanism and stability, distinguishing lantibiotics from other peptides.

In scientific literature, lanthionine is discussed as a key structural motif within lantibiotics rather than as a free amino acid in proteins. Its presence helps explain the characteristic chemistry, biosynthesis, and biological activity of these peptides.