Lanthipeptides
are ribosomally synthesized and post-translationally
modified peptides (RiPPs) that display a wide variety of biological
activities, from antimicrobial to antiallodynic. Lanthipeptides that
display antimicrobial activity are called lantibiotics. The post-translational
modification reactions of lanthipeptides include dehydration of Ser
and Thr residues to dehydroalanine and dehydrobutyrine, a transformation
that is carried out in three unique ways in different classes of lanthipeptides.
In a cyclization process, Cys residues then attack the dehydrated
residues to generate the lanthionine and methyllanthionine thioether
cross-linked amino acids from which lanthipeptides derive their name.
The resulting polycyclic peptides have constrained conformations that
confer their biological activities. After installation of the characteristic
thioether cross-links, tailoring enzymes introduce additional post-translational
modifications that are unique to each lanthipeptide and that fine-tune
their activities and/or stability. This review focuses on studies
published over the past decade that have provided much insight into
the mechanisms of the enzymes that carry out the post-translational
modifications.