Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with four sulphide-rings

Abstract

The genetic basis for the biosynthesis of large polypeptide antibiotics such as nisin has not been explained so far. We show here that the structural gene epiA encoding the antibiotic epidermin from Staphylococcus epidermidis is located on a 54-kilobase plasmid and codes for a 52-amino-acid prepeptide, which is processed to the tetracyclic 21-peptide amide antibiotic. The mature sequence of epidermin corresponds to the C-terminal 22-peptide segment of pre-epidermin and contains the precursor amino acids Ser, Thr and Cys, from which the unusual amino-acid constituents are derived. The more lipophilic epidermin is cleaved at a hydrophilic turn between Arg-1 and Ile+1 from the N-terminal segment-30 to -1, which probably assumes a partially amphiphilic alpha-helix conformation. We propose that the N-terminus (-30 to -1) plays a cooperative role during modification reactions and prevents toxicity of the mature epidermin to the producing strain before the antibiotic is cleaved off and secreted.

Pheromone‐induced production of antimicrobial peptides in Lactobacillus

“…Bacteriocins generally contain between 30 and 60 residues, and they are mostly basic. Some bacteriocins contain post-translationally modified amino acids and are called lantibiotics (Schnell et al, 1988). Secretion of bacteriocins is directed by a leader peptide that is cleaved off during or after export.…”

Protein engineering of lantibiotics

“…The cloning and sequencing of the first structural lantibiotic gene in 1988 (Schnell et al 1988;Banerjee & Hansen 1988) and the very rapidly expanding number of other lantibiotic gene sequences, has stimulated intensive research towards the organization of gene clusters and elucidation of the biosynthetic pathways of lantibiotics. Moreover, it enabled a protein engineering approach as a powerful tool to identify lantibiotic structural elements important for antimicrobial activity and biosynthesis.…”

Characterization of the nisin gene cluster nisABTCIPR of Lactococcus lactis

“…Nisin is produced by several strains of the Gram-positive bacterium Lactococcus lactis and is applied in the food industry as a natural preservative because it effectively inhibits the growth of food spoilage bacteria (Delves-Broughton, 1990). The biosynthesis of nisin and other lantibiotics is thought to take place by successive enzyme-catalyzed modifications of the ribosomally synthesized precursor peptide (Schnell et al, 1988). These specific modifications of precursor nisin include the following: dehydration of serine and threonine residues, resulting in dehydroalanine and dehydrobutyrine residues, respectively ; the addition of free thiol groups of cysteine residues to the double bonds of dehydrated residues, resulting in meso-lanthionine and P-methyllanthionine residues; cleavage of the leader peptide from the mature precursor nisin after secretion into the medium (van der Meer et al, 1993).…”

“…The antimicrobial peptide nisin (Gross and Morell, 1971 ;Hurst, 1981) belongs to the rapidly expanding family of lantibiotics (Schnell et al, 1988), a group of small peptides (less than 4 kDa), which contain (P-methy1)lanthionine residues. Nisin is produced by several strains of the Gram-positive bacterium Lactococcus lactis and is applied in the food industry as a natural preservative because it effectively inhibits the growth of food spoilage bacteria (Delves-Broughton, 1990).…”