Lanthionine

In 1941, lanthionine was first isolated by treating wool with sodium carbonate. It was found to be a sulfur-containing amino acid; accordingly it was given the name lanthionine [wool (Latin: Lana), sulfur (Greek: theîon)]. Lanthionine was first synthesized by alkylation of cysteine with β-chloroalanine. Lanthionines are found widely in nature. They have been isolated from human hair, lactalbumin, and feathers. Lanthionines have also been found in bacterial cell walls and are the components of a group of gene-encoded peptide antibiotics called lantibiotics, which includes nisin (a food preservative), subtilin, epidermin (effective against Staphylococcus and Streptococcus), and ancovenin (an enzyme inhibitor). Lanthionine is listed among novel uremic toxins, compounds elevated in blood of chronic kidney failure and uremic patiens. It likely contributes to hyperhomocysteinemia and impaired hydrogen sulfide biosynthesis. Lanthionine retention may also be linked to adverse cardiovascular outcomes as it can induce heart tissue fibrosis and promote vascular calcification.

A variety of syntheses of lanthionine have been published including sulfur extrusion from cystine, ring opening of serine β-lactone, and hetero-conjugate addition of cysteine to dehydroalanine. The sulfur extrusion method is, however, the only pathway for lanthionine that has been employed in the total synthesis of a lantibiotic.

Biosynthesis of the lanthionine bridge in peptidic natural products can be accomplished through a number of different pathways. For example, the lanthionine bridges in the antibiotic nisin are the result of a dedicated dehydratase (NisB) and a dedicated cyclase (NisC).