CHAPTER 5 - The Molecular Biology of Nisin and Its Structural Analogues

Abstract

This chapter discusses the molecular biology of nisin and its structural analogues. Nisin is a bacterially produced peptide that contains an inordinate proportion of unusual amino acids. The mature nisin structure contains dehydroalanine, dehydrobutyrine, lanthionine, and ß-methyllanthionine. Nisin is an example of a class of ribosomally synthesized peptide antibiotics. The existence of nisin and the several other ribosomally synthesized lantibiotics shows that some biological systems can introduce new amino acids in a controlled manner into what would otherwise be ordinary peptides. The advantage of the lantibiotics is that their structures are unambiguously dictated by genes. Unlike most antibiotics synthesized by multienzyme metabolic pathways, the fact that lantibiotics are gene encoded and synthesized ribosomally means it is possible to make specific structural alterations in the mature lantibiotic by mutating the precursor gene. Nisinbiosynthesis is synthesized as a precursor consisting of a 23-residue leader region and a 34-residue structural region. The leader region is excised, the structural region undergoes posttranslational modifications, and mature nisin is secreted outside the cell. However, nisin and other lantibiotics are still in the infancy of their development. The increase in the number of laboratories studying them creates confidence that the fundamentals of their molecular biology, mechanism of biosynthesis, and mechanism of action will be elucidated within a few years.