Major gene‐regulatory mechanisms operating in ribosomally synthesized and post‐translationally modified peptide (RiPP) biosynthesis

Bartholomae, Maike; Buivydas, Andrius; Viel, Jakob; Montalbán-López, Manuel; Kuipers, Oscar P.

doi:10.1111/mmi.13764

Cited by 26 publications

(18 citation statements)

References 193 publications

(241 reference statements)

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“…While genes encoding proteins that are commonly involved in the regulation of most bacteriocins such as histidine kinase and response regulator proteins were found in the vicinity of the biosynthetic gene clusters of some circular bacteriocins such as that of butyrivibriocin AR10, circularin, uberolysin, and enterocin NKR-5-3B, their cognate activator molecules have not been identified. Nonetheless, some hints pointing to the possible regulation by quorum sensing three component system are apparent ( Bartholomae et al, 2017 ).…”

Section: Circular Bacteriocinsmentioning

confidence: 99%

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

2018

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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.

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Section: Circular Bacteriocinsmentioning

confidence: 99%

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

2018

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“…coelicolor 356 . For a detailed overview on the regulation of RiPPs in Actinobacteria and other bacterial genera, we refer the reader a recent review 357 .…”

Section: Control Of Glycopeptide Resistancementioning

confidence: 99%

Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era

et al. 2018

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Covering: 2000 to 2018 The antimicrobial activity of many of their natural products has brought prominence to the Streptomycetaceae, a family of Gram-positive bacteria that inhabit both soil and aquatic sediments. In the natural environment, antimicrobial compounds are likely to limit the growth of competitors, thereby offering a selective advantage to the producer, in particular when nutrients become limited and the developmental programme leading to spores commences. The study of the control of this secondary metabolism continues to offer insights into its integration with a complex lifecycle that takes multiple cues from the environment and primary metabolism. Such information can then be harnessed to devise laboratory screening conditions to discover compounds with new or improved clinical value. Here we provide an update of the review we published in NPR in 2011. Besides providing the essential background, we focus on recent developments in our understanding of the underlying regulatory networks, ecological triggers of natural product biosynthesis, contributions from comparative genomics and approaches to awaken the biosynthesis of otherwise silent or cryptic natural products. In addition, we highlight recent discoveries on the control of antibiotic production in other Actinobacteria, which have gained considerable attention since the start of the genomics revolution. New technologies that have the potential to produce a step change in our understanding of the regulation of secondary metabolism are also described.

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“…Given their high sequence identities to each other, it is clear they are a result of duplication events in which slight variants with independent promoters have been selected for. It is most likely that these strains swap or co-express variable circular bacteriocins via response regulators and quorum sensing [29,31,71], allowing expression of different circular bacteriocins with a slightly different spectrum of activity/microbial targets. These multi-structural gene clusters can also give us insights into the putative immunity genes.…”

Section: Conserved Genes Within Circular Bacteriocin Clustersmentioning

confidence: 99%

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

2020

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Background: Circular bacteriocins are antimicrobial peptides produced by bacteria with a N and C termini ligation. They have desirable properties such as activity at low concentrations along with thermal, pH and proteolytic resistance. There are twenty experimentally confirmed circular bacteriocins as part of bacteriocin gene clusters, with transport, membrane and immunity proteins. Traditionally, novel antimicrobials are found by testing large numbers of isolates against indicator strains, with no promise of corresponding novel sequence. Results: Through bioprospecting publicly available sequence databases, we identified ninety-nine circular bacteriocins across a variety of bacteria bringing the total to 119. They were grouped into two families within class I modified bacteriocins (i and ii) and further divided into subfamilies based on similarity to experimentally confirmed circular bacteriocins. Within subfamilies, sequences overwhelmingly shared similar characteristics such as sequence length, presence of a polybasic region, conserved locations of aromatic residues, C and N termini, gene clusters similarity, translational coupling and hydrophobicity profiles. At least ninety were predicted to be putatively functional based on gene clusters. Furthermore, bacteriocins identified from Enterococcus, Staphylococcus and Streptococcus species may have activity against clinically relevant strains, due to the presence of putative immunity genes required for expression in a toxin-antitoxin system. Some strains such as Paenibacillus larvae subsp. pulvifaciens SAG 10367 contained multiple circular bacteriocin gene clusters from different subfamilies, while some strains such as Bacillus cereus BCE-01 contained clusters with multiple circular bacteriocin structural genes. Conclusions: Sequence analysis provided rapid insight into identification of novel, putative circular bacteriocins, as well as conserved genes likely essential for circularisation. This represents an expanded library of putative antimicrobial proteins which are potentially active against human, plant and animal pathogens.

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Major gene‐regulatory mechanisms operating in ribosomally synthesized and post‐translationally modified peptide (RiPP) biosynthesis

Cited by 26 publications

References 193 publications

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

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

Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era

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

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