Abstract
Lanthipeptides are ribosomally synthesized and post-translationally modified polycyclic peptides. Lanthipeptides that have antimicrobial activity are known as lantibiotics. Accordingly, the discovery of novel lantibiotics constitutes a possible solution for the problem of antibiotic resistance. We utilized the publicly available genome sequences and the bioinformatic tools tailored for the detection of lanthipeptides. We designed our strategy for screening of 252 firmicute genomes and detecting class-I lanthipeptide-coding gene clusters. The designed strategy resulted in identifying 69 class-I lanthipeptide sequences, of which more than 10% were putative novel. The identified putative novel lanthipeptides have not been annotated on the original or the RefSeq genomes, or have been annotated merely as coding for hypothetical proteins. Additionally, we identified bacterial strains that have not been previously recognized as lanthipeptide-producers. Moreover, we suggest corrections for certain firmicute genome annotations, and recommend lanthipeptide records for enriching the bacteriocin genome mining tool (BAGEL) databases. Furthermore, we propose Z-geobacillin, a putative class-I lanthipeptide coded on the genome of the thermophilic strain Geobacillus sp. ZGt-1. We provide lists of putative novel lanthipeptide sequences and of the previously unrecognized lanthipeptide-producing bacterial strains, so they can be prioritized for experimental investigation. Our results are expected to benefit researchers interested in the in vitro production of lanthipeptides.
Highlights
In parallel with the continuously growing problem of bacterial multidrug resistance together with the customer requirements for using natural antimicrobial compounds and food preservatives in food products, there is a growing need for identifying new natural antimicrobial compounds, among which is the family of lanthipeptides.Lanthipeptides are ribosomally synthesized cyclic peptides, distinguished by the presence of unusual thioether-linked amino acids, lanthionine (Lan) and (2S,3S,6R)-3-methyllanthionine (MeLan) [1]
The strategy we plotted for identifying class-I lanthipeptides started with downloading the complete genome sequences of firmicute bacterial strains deposited in the Reference Sequence (RefSeq) genome database (Figure 1)
In addition to the 69 identified lanthipeptides, we propose the lanthipeptide Z-geobacillin predicted to be produced by the novel Geobacillus sp. strain ZGt-1 which we isolated from Zara hot spring in Jordan [21,22] as a putative novel lanthipeptide (Table 1; Table S1), and hereby we report it and describe its biosynthesis gene cluster
Summary
In parallel with the continuously growing problem of bacterial multidrug resistance together with the customer requirements for using natural antimicrobial compounds and food preservatives in food products, there is a growing need for identifying new natural antimicrobial compounds, among which is the family of lanthipeptides.Lanthipeptides are ribosomally synthesized cyclic peptides, distinguished by the presence of unusual thioether-linked amino acids, lanthionine (Lan) and (2S,3S,6R)-3-methyllanthionine (MeLan) [1]. The lanthipeptide is synthesized as a precursor peptide (generally designated as LanA) that undergoes post-translational modifications to produce the bioactive mature lanthipeptide. The modifications involve dehydration of serine (Ser) and threonine (Thr) residues to dehydroalanine (Dha) and dehydrobutyrine (Dhb), respectively, followed by addition of the thiol groups of cysteine (Cys) residues onto Dha and Dhb which results in the formation of thioether cross-links, yielding the Lan and MeLan residues, respectively [1]. Lanthipeptides are classified based on the biosynthetic enzymes involved in the post-translational modifications into four classes [1]. The post-translational modifications take place in the core-peptide which gives the bioactive mature peptide [2]. The leader peptide is cleaved off either intracellularly or extracellularly by a lanthipeptide-dedicated serine protease (LanP) or by another protease produced by the host cell [2].
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