Abstract
Lantibiotics are ribosomally-synthesized and posttranslationally modified peptides with potent antimicrobial activities. Discovery of novel lantibiotics has been greatly accelerated with the soaring release of genomic information of microorganisms. As a unique class II lantibiotic, bovicin HJ50 is produced by Streptococcus bovis HJ50 and contains one rare disulfide bridge. By using its precursor BovA as a drive sequence, 16 BovA-like peptides were revealed in a wide variety of species. From them, three representative novel lan loci from Clostridium perfringens D str. JGS1721, Bacillus cereus As 1.348 and B. thuringiensis As 1.013 were identified by PCR screening. The corresponding mature lantibiotics designated perecin, cerecin and thuricin were obtained and structurally elucidated to be bovicin HJ50-like lantibiotics especially by containing a conserved disulfide bridge. The disulfide bridge was substantiated to be essential for the function of bovicin HJ50-like lantibiotics as its disruption eliminated their antimicrobial activities. Further analysis indicated that the disulfide bridge played a crucial role in maintaining the hydrophobicity of bovicin HJ50, which might facilitate it to exert antimicrobial function. This study unveiled a novel subgroup of disulfide-containing lantibiotics from bacteria of different niches and further demonstrated the indispensable role of disulfide bridge in these novel bovicin HJ50-like lantibiotics.
Highlights
Disulfide bridges especially intramolecular disulfide linkages are prevalent in antimicrobial peptides and have been acknowledged to play important roles in biological function either by dictating the complex structural conformation or maintaining stability
By using bovicin HJ50 precursor BovA as a drive sequence, more than 16 BovA-like proteins had been revealed from publicly available genomes of streptococci, enterococci, clostridium and bacilli in NCBI database (Table S1)
These BovA-like peptides are small in size (,55aa) and display more than 36% identities with BovA. They all contain a typical class II lantibiotic leader peptide with a GG motif for cleavage to release mature lantibiotics and the putative core peptides are conserved in residual positions of two dehydratable Thr and four ring-forming Cys as bovicin HJ50 (Figure S1)
Summary
Disulfide bridges especially intramolecular disulfide linkages are prevalent in antimicrobial peptides and have been acknowledged to play important roles in biological function either by dictating the complex structural conformation or maintaining stability. As a large member of bacteriocins, lantibiotics are posttranslationally modified peptides mainly containing lanthioine (Lan) and methyllanthioine (MeLan) residues [5,6]. These unusual residues are introduced by lanthionine synthetases, based on which lantibiotics are classified into four classes (I to IV) [6]. The enzyme(s) involved in disulfide bridge formation was not identified in gene clusters responsible for lantibiotic synthesis The function of these disulfide bridges have not been fully investigated and were indicated to be of minor importance to biological activities [7,10,11]
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