Maturation pathway of nisin and other lantibiotics: post‐translationally modified antimicrobial peptides exported by Gram‐positive bacteria

Abstract

SummaryLantibiotics form a family of highly modified peptides which are secreted by several Gram-positive bacteria. They exhibit antimicrobial activity, mainly against other Gram-positive bacteria, by forming pores in the cellular membrane. These antimicrobial peptides are ribosomally synthesized and contain leader peptides which do not show the characteristics of signal sequences. Several amino acid residues of the precursor lantibiotic are enzymatically modified, whereafter secretion and processing of the leader peptide takes place, yielding the active antimicrobial substance. For several lantibiotics the gene clusters encoding biosynthetic enzymes, translocator proteins, self-protection proteins, processing enzymes and regulatory proteins have been identified. This MicroReview describes the current knowledge about the biosynthetic, immunity and regulatory processes leading to lantibiotic production. Most of the attention is focused on the lantibiotic nisin, which is produced by the food-grade bacterium Lactococcus lactis and is widely used as a preservative in the food industry.

Identification of the Nukacin KQU-131, a New Type-A(II) Lantibiotic Produced byStaphylococcus hominisKQU-131 Isolated from Thai Fermented Fish Product (Pla-ra)

“…6) The type-A group is further divided into two subgroups, type-A(I) and type-A(II), based on the sizes, charges, and sequences of the leader peptides. 7) The biosynthetic pathway for the lantibiotics is as follows: [4][5][6][7] First, the lantibiotic prepeptide LanA, which consists of an N-terminal leader peptide followed by a C-terminal propeptide, is ribosomally synthesized. In the biosynthesis of type-A(I) lantibiotics, LanB and LanC are required for the dehydration of serines and threonines and the coupling of cysteines to dehydroresidues (cyclization) respectively.…”

Inducible gene expression and environmentally regulated genes in lactic acid bacteria

“…Apparently, nisin or one of its precursors is required for transcription of its own gene. In a follow-up study (Kuipers et al, 1995), this phenomenon was further analyzed. Northern blotting using mRNA from the AnisA strain revealed that, indeed, AnisA transcription was restored upon addition of nisin to the culture medium.…”

“…These proteins belong to the class of two-component regulatory systems in which, in this case, NisR is the response regulator and NisK the signal sensor or sensor histidine kinase (for excellent reviews, see Schnell et al, 1988;Jung 1991;Sahl et al, 1995;de Vos et al, 1995). Three promoters, upstream of nisA, nisR and nisF, have been mapped by primer extension (Kuipers et al, 1993;Kuipers et al, 1995;de Ruyter et al, 1996;P. Saris, pers.…”

Quorum Sensing within the Gut Ecosystem

“…It appears that Gram-positive bacteria prefer peptide signals, also termed peptide pheromones (5). These peptides are processed during secretion but may also be subject to complex post-translational modi cations such as nisin in lactococci (6) or peptide thiolactones in staphylococci (7). Although there are, as yet, no chemically characterized examples of quorum sensing signal molecules common to both Gram-negative and Gram-positive bacteria, a gene termed luxS has been identi ed which has homologues in both types of bacteria (8).…”