Lantibiotics and microcins: Novel posttranslational modifications of polypeptides

Abstract

Unique peptide modification mechanisms have attracted considerable interest from scientists working in both applied and basic research. The design, genetic engineering and production of unusually modified peptides for use in areas such as biomedical applications and food technology has rapidly become a small, but exciting, new branch of biotechnology. Both lantibiotics and microcins are antimicrobial peptides which contain combinations of thioether bridges, α,β-unsaturated amino acids, D-amino acids, N-, C-terminal and heteroaromatic backbone modifications, all of which arise from posttranslational modifications of Ser, Thr, Cys and Gly residues in a ribosomally-synthesised precursor polypeptide. The structures of many of the lantibiotics have been elucidated and the structure of 13C-,15N-labelled microcin B17 has been solved. In addition, the total synthesis of microcin B17, and a number of analogues, was recently accomplished. The previously undescribed enzymes apparently responsible for dehydration, ring formation, oxidative decarboxylation, hydrogenation, and leader peptide cleavage are currently being characterised.