Chapter 16 - Lantibiotics

Abstract

This chapter focuses on lantibiotics that are lanthionine-containing antibiotic peptides. Lantibiotics derive from ribosomally synthesized prepeptides through unique posttranslational modifications involving serine, threonine, and cysteine residues. Approximately 50 lantibiotics are known to date, and almost 20 gene clusters, containing the determinants for prepeptides, modification, and processing, export, and producer self-protection have been sequenced. Genetic determinants for lantibiotic synthesis are exclusively found among gram-positive bacteria and can be located either on chromosomes or on mobile elements such as plasmids and transposons. The antimicrobial activity of lantibiotics does not involve receptors sensu strictu, although specific targets have been identified. However, lantibiotic biosynthesis may be autoregulated through a quorum sensing process, in which the respective lantibiotic acts as an upregulating signal. In this case, the lantibiotic binds to a receptor that is the histidine kinase of a dedicated two-component regulatory system. Lantibiotics are active against gram-positive bacteria and exert multiple activities at the cytoplasmic membrane. Recent advancements in in vitro synthesis and insights into multiple antibiotic mechanisms combined in a single molecule can make lantibiotics an attractive model compounds for design of novel anti-infective drugs.