Lantibiotics and microcins: polypeptides with unusual chemical diversity

Bacterial-derived antimicrobial polypeptides enjoy a large degree of struct ural and chemical diversity. Two well-studied examples of such polypeptides are the lanthionine-containing lantibiotics produced by a variety of Gram- positive bacteria, and their Gram-negative counterparts, the microcins. Bot h groups are produced as gene-encoded precursor peptides and undergo post-t ranslational modification to generate the active moieties. Structure elucid ation of novel lantibiotics and microcins has recently uncovered further no vel structural and chemical features and, combined with the generation of a nalogue peptides by genetic manipulation, new insights into structure-funct ion relationships have been gained. Furthermore, study of the mode of actio n of the antibiotics nisin and mersacidin has revealed their use of a 'dock ing molecule' in the target cell to facilitate their biological activities. Meanwhile, in vitro studies with microcin B17 have helped to uncover the m olecular mechanisms by which post-translational modification results in the formation of heterocyclic oxazole and thiazole rings. From a practical sta ndpoint, bath groups of polypeptides represent new lead structures for futu re development of antimicrobial agents, whilst the identification of the 'd ocking molecules' represents a step forward in the search for novel targets for future antibiosis.