Circular and Leaderless Bacteriocins: Biosynthesis, Mode of Action, Applications, and Prospects

Abstract

Bacteriocins are a huge family of ribosomally synthesized peptides known to exhibit a range of bioactivities, most predominantly antibacterial activities. Bacteriocins from lactic acid bacteria are of particular interest due to the latter’s association to food fermentation and the general notion of them to be safe. Among the family of bacteriocins, the groups known as circular bacteriocins and leaderless bacteriocins are gaining more attention due to their enormous potential for industrial application. Circular bacteriocins and leaderless bacteriocins, arguably the least understood groups of bacteriocins, possess distinctively peculiar characteristics in their structures and biosynthetic mechanisms. Circular bacteriocins have N-to-C- terminal covalent linkage forming a structurally distinct circular peptide backbone. The circular nature of their structures provides them superior stability against various stresses compared to most linear bacteriocins. The molecular mechanism of their biosynthesis, albeit has remained poorly understood, is believed to possesses huge application prospect as it can serve as scaffold in bioengineering other biologically important peptides. On the other hand, while most bacteriocins are synthesized as inactive precursor peptides, which possess an N-terminal leader peptide attached to a C-terminal propeptide, leaderless bacteriocins are atypical as they do not have an N-terminal leader peptide, hence the name. Leaderless bacteriocins are active right after translation as they do not undergo any post-translational processing common to other groups of bacteriocins. This “simplicity” in the biosynthesis of leaderless bacteriocins offers a huge commercial potential as scale-up production systems are considerably easier to assemble. In this review, we summarize the current studies of both circular and leaderless bacteriocins, highlighting the progress in understanding their biosynthesis, mode of action, application and their prospects.

Bioinformatic prospecting and phylogenetic analysis reveals 94 undescribed circular bacteriocins and key motifs

“…This study shows that circular bacteriocins are much more prevalent than originally expected [39]. Previous bioinformatics efforts have identified uncharacterised novel circular bacteriocins [28,30].…”

“…S1), contain putatively functional circular bacteriocin clusters. This indicates a potentially large reservoir of circular bacteriocin-producing strains and circular bacteriocins which could be used as therapeutics, food preservatives [39], or in other applications such as use as vector proteins to stabilise bioactive proteins [56]. There are many bioactive peptides which report low stability [57], which could be stabilised with C-N terminal ligation [58] found in circular bacteriocins.…”

“…Phylogenetic classification has resolution trade-offs. A higher number of families (reasonably up to 6) could have been attributed, though due to the similar proposed modes of action [17,39] and conserved structural motifs [11,30,34,35], further familial division would result in diminished returns. By classifying circular bacteriocins into groups with higher resolution such as subfamilies, experimentally-confirmed circular bacteriocins can be used as type-sequences and accurate sequence analysis and comparisons can be performed.…”

“…A pre-peptide encoded by the bacteriocin structural gene is produced, followed by signal sequence/leader peptide cleavage. This mature peptide is then able to be either circularised within the cell then secreted which has been shown for leucocyclin Q [38], or secreted and then circularised [39]. The genes involved and the process are not well understood, and it's possible that different pathways exist for different circular bacteriocins.…”

Cloning and functional expression of a food-grade circular bacteriocin, plantacyclin B21AG, in probioticLactobacillus plantarumWCFS1

“…These antimicrobial peptides appear to have great potential in food preservation, particularly in controlling food-borne pathogens. Discovery of more circular bacteriocins is highly favourable over linear peptides due to their superior stability against various stresses [26].…”