Lantibiotics : An Overview and Conformational Studies on Gallidermin and Pep5

Abstract

Lantibiotics are polycyclic bacteriocins with the thioether amino acids lanthionine and β - methyllanthionine. In addition to these intrachain sulfide bridges, unsaturated amino acids like α,β- didehydroalanine and α, β - didehydrobutyric acid occur. Members of the lantibiotics family are for example nisin, an important food preservative, epidermin, a highly specific therapeutic drug against acne, a series of enzyme inhibitors and immunologically interesting peptides such as the duramycins. In recent years, an increasing number of novel lantibiotics has been discovered. Lantibiotics are produced via ribosomal synthesis from inactive precursor proteins (prelantibiotics), which are post-translationally converted to the biologically active polycyclic peptides. The enzyme involved herein catalyzes the dehydration of the serine and threonine residues to yield unsaturated residues. This step is followed by a stereospecific addition of the cysteine thiol groups to these double bonds leading to the formation of sulfide bridges. The final step is the release of the active peptide by proteolytic cleavage of the leader peptide. Conformational analysis of the lantibiotics, as well as their prepeptides, provide information about their mode of action and the steps of biosynthesis. Based on the knowledge of the lantibiotic biosynthesis, and by using the isolated novel enzymes, a gene technological construction of a variety of similarly modified polypeptides will be available in the near future.