In silico analysis highlights the frequency and diversity of type 1 lantibiotic gene clusters in genome sequenced bacteria.

Alan J Marsh,R Paul Ross,Colin Hill,Paul D Cotter,Orla O'Sullivan

doi:10.1186/1471-2164-11-679

Abstract

BackgroundLantibiotics are lanthionine-containing, post-translationally modified antimicrobial peptides. These peptides have significant, but largely untapped, potential as preservatives and chemotherapeutic agents. Type 1 lantibiotics are those in which lanthionine residues are introduced into the structural peptide (LanA) through the activity of separate lanthionine dehydratase (LanB) and lanthionine synthetase (LanC) enzymes. Here we take advantage of the conserved nature of LanC enzymes to devise an in silico approach to identify potential lantibiotic-encoding gene clusters in genome sequenced bacteria.ResultsIn total 49 novel type 1 lantibiotic clusters were identified which unexpectedly were associated with species, genera and even phyla of bacteria which have not previously been associated with lantibiotic production.ConclusionsMultiple type 1 lantibiotic gene clusters were identified at a frequency that suggests that these antimicrobials are much more widespread than previously thought. These clusters represent a rich repository which can yield a large number of valuable novel antimicrobials and biosynthetic enzymes.

Highlights

Lantibiotics are lanthionine-containing, post-translationally modified antimicrobial peptides
The majority of the class I bacteriocins are lantibiotics; small peptides containing internal bridges resulting from the formation of (b-methyl)lanthionine residues
In silico screen for lanC genes An in silico screen for LanC homologues, using the NisC sequence as a driver, resulted in the identification of 56 homologues. Of these 7 have previously been associated with lantibiotic production, 11 were orphan homologs (Table 1), 9 were encoded within a cluster in which no lanA could be detected (Table 2) and one cluster contained two LanCs

Summary

Introduction

Lantibiotics are lanthionine-containing, post-translationally modified antimicrobial peptides. These peptides have significant, but largely untapped, potential as preservatives and chemotherapeutic agents. The majority of the class I bacteriocins are lantibiotics; small peptides containing internal bridges resulting from the formation of (b-methyl)lanthionine residues. The structural gene encodes a ribosomally synthesised precursor prepeptide which is generically named LanA This prepeptide contains a leader sequence at the N-terminus, which is cleaved, and a propeptide at the C-terminus. Many or all of the serine and threonine residues within the propeptide are dehydrated to form dehydroalanine (Dha) and dehydrobutyrine (Dhb), respectively When these modified residues interact with an intrapeptide cysteine, a thioether bond is formed resulting in the formation of lanthionine (Lan, from Dha) or b-methyl lanthionine (meLan, from Dhb)

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Conclusion