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Genome mining for ribosomally synthesized and post-translationally modified peptides (RiPPs) in anaerobic bacteria.

Letzel AC, Pidot SJ, Hertweck C - BMC Genomics (2014)

Bottom Line: More than 25% of anaerobes are capable of producing RiPPs either alone or in conjunction with other secondary metabolites, such as polyketides or non-ribosomal peptides.Amongst the analyzed genomes, several gene clusters encode uncharacterized RiPPs, whilst others show similarity with known RiPPs.These include a number of potential class II lanthipeptides; head-to-tail cyclized peptides and lactococcin 972-like RiPP.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute for Natural Product Research and Infection Biology HKI, Beutenbergstr, 11a, Jena 07745, Germany. christian.hertweck@hki-jena.de.

ABSTRACT

Background: Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a diverse group of biologically active bacterial molecules. Due to the conserved genomic arrangement of many of the genes involved in their synthesis, these secondary metabolite biosynthetic pathways can be predicted from genome sequence data. To date, however, despite the myriad of sequenced genomes covering many branches of the bacterial phylogenetic tree, such an analysis for a broader group of bacteria like anaerobes has not been attempted.

Results: We investigated a collection of 211 complete and published genomes, focusing on anaerobic bacteria, whose potential to encode RiPPs is relatively unknown. We showed that the presence of RiPP-genes is widespread among anaerobic representatives of the phyla Actinobacteria, Proteobacteria and Firmicutes and that, collectively, anaerobes possess the ability to synthesize a broad variety of different RiPP classes. More than 25% of anaerobes are capable of producing RiPPs either alone or in conjunction with other secondary metabolites, such as polyketides or non-ribosomal peptides.

Conclusion: Amongst the analyzed genomes, several gene clusters encode uncharacterized RiPPs, whilst others show similarity with known RiPPs. These include a number of potential class II lanthipeptides; head-to-tail cyclized peptides and lactococcin 972-like RiPP. This study presents further evidence in support of anaerobic bacteria as an untapped natural products reservoir.

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Detected putative LAP gene cluster. A Gene cluster of plantazolicin (pzn) (B. amyloliquefeaciens FZB42), streptolysin S (sag) (S. pyrogenes) and clostridiolysin S (clos) (C. botulinum ATCC 3502) in comparison to putative LAP gene clusters of B. intermedia, B. hyodysenteriae and T. mathranii mathranii A3; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Comparison of precursor peptides of plantazolicin (PlnA), streptolysin S (SagA), clostridiolysin S (ClosA) with putative precursor peptides of B. intermedia, B. hyodysenteriae, and T. mathranii mathranii A3; Cleavage site of leader and core peptide in bold. C Introduction of heterocycles in plantazolicin by cyclodehydrogenase (PznC) and dehydrogenase (PznB) enzyme complex, X = S,O. D Chemical structure of plantazolicin.
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Fig6: Detected putative LAP gene cluster. A Gene cluster of plantazolicin (pzn) (B. amyloliquefeaciens FZB42), streptolysin S (sag) (S. pyrogenes) and clostridiolysin S (clos) (C. botulinum ATCC 3502) in comparison to putative LAP gene clusters of B. intermedia, B. hyodysenteriae and T. mathranii mathranii A3; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Comparison of precursor peptides of plantazolicin (PlnA), streptolysin S (SagA), clostridiolysin S (ClosA) with putative precursor peptides of B. intermedia, B. hyodysenteriae, and T. mathranii mathranii A3; Cleavage site of leader and core peptide in bold. C Introduction of heterocycles in plantazolicin by cyclodehydrogenase (PznC) and dehydrogenase (PznB) enzyme complex, X = S,O. D Chemical structure of plantazolicin.

Mentions: Many RiPPs are characterized by the presence of heterocyclic functional groups, such as oxazoles and thiazoles. One such group are the linear azol(in)e-containing peptides (LAP), whose heterocycles are derived from the cysteine, serine and threonine of a small precursor peptide[1]. LAP comprise of four essential components: a precursor peptide (known as ‘A’), and a heterotrimeric enzyme complex consisting of a dehydrogenase (‘B’) and cyclodehydratase (‘C’ and ‘D’). Biosynthetically, the first step towards a LAP is the formation of an azoline-heterocycle by the ‘C/D’ complex from serine or threonine and a cysteine residue, followed by dehydrogenation by ‘B’ leading to the corresponding azole (Figure 6C).Figure 6


Genome mining for ribosomally synthesized and post-translationally modified peptides (RiPPs) in anaerobic bacteria.

Letzel AC, Pidot SJ, Hertweck C - BMC Genomics (2014)

Detected putative LAP gene cluster. A Gene cluster of plantazolicin (pzn) (B. amyloliquefeaciens FZB42), streptolysin S (sag) (S. pyrogenes) and clostridiolysin S (clos) (C. botulinum ATCC 3502) in comparison to putative LAP gene clusters of B. intermedia, B. hyodysenteriae and T. mathranii mathranii A3; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Comparison of precursor peptides of plantazolicin (PlnA), streptolysin S (SagA), clostridiolysin S (ClosA) with putative precursor peptides of B. intermedia, B. hyodysenteriae, and T. mathranii mathranii A3; Cleavage site of leader and core peptide in bold. C Introduction of heterocycles in plantazolicin by cyclodehydrogenase (PznC) and dehydrogenase (PznB) enzyme complex, X = S,O. D Chemical structure of plantazolicin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4289311&req=5

Fig6: Detected putative LAP gene cluster. A Gene cluster of plantazolicin (pzn) (B. amyloliquefeaciens FZB42), streptolysin S (sag) (S. pyrogenes) and clostridiolysin S (clos) (C. botulinum ATCC 3502) in comparison to putative LAP gene clusters of B. intermedia, B. hyodysenteriae and T. mathranii mathranii A3; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Comparison of precursor peptides of plantazolicin (PlnA), streptolysin S (SagA), clostridiolysin S (ClosA) with putative precursor peptides of B. intermedia, B. hyodysenteriae, and T. mathranii mathranii A3; Cleavage site of leader and core peptide in bold. C Introduction of heterocycles in plantazolicin by cyclodehydrogenase (PznC) and dehydrogenase (PznB) enzyme complex, X = S,O. D Chemical structure of plantazolicin.
Mentions: Many RiPPs are characterized by the presence of heterocyclic functional groups, such as oxazoles and thiazoles. One such group are the linear azol(in)e-containing peptides (LAP), whose heterocycles are derived from the cysteine, serine and threonine of a small precursor peptide[1]. LAP comprise of four essential components: a precursor peptide (known as ‘A’), and a heterotrimeric enzyme complex consisting of a dehydrogenase (‘B’) and cyclodehydratase (‘C’ and ‘D’). Biosynthetically, the first step towards a LAP is the formation of an azoline-heterocycle by the ‘C/D’ complex from serine or threonine and a cysteine residue, followed by dehydrogenation by ‘B’ leading to the corresponding azole (Figure 6C).Figure 6

Bottom Line: More than 25% of anaerobes are capable of producing RiPPs either alone or in conjunction with other secondary metabolites, such as polyketides or non-ribosomal peptides.Amongst the analyzed genomes, several gene clusters encode uncharacterized RiPPs, whilst others show similarity with known RiPPs.These include a number of potential class II lanthipeptides; head-to-tail cyclized peptides and lactococcin 972-like RiPP.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute for Natural Product Research and Infection Biology HKI, Beutenbergstr, 11a, Jena 07745, Germany. christian.hertweck@hki-jena.de.

ABSTRACT

Background: Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a diverse group of biologically active bacterial molecules. Due to the conserved genomic arrangement of many of the genes involved in their synthesis, these secondary metabolite biosynthetic pathways can be predicted from genome sequence data. To date, however, despite the myriad of sequenced genomes covering many branches of the bacterial phylogenetic tree, such an analysis for a broader group of bacteria like anaerobes has not been attempted.

Results: We investigated a collection of 211 complete and published genomes, focusing on anaerobic bacteria, whose potential to encode RiPPs is relatively unknown. We showed that the presence of RiPP-genes is widespread among anaerobic representatives of the phyla Actinobacteria, Proteobacteria and Firmicutes and that, collectively, anaerobes possess the ability to synthesize a broad variety of different RiPP classes. More than 25% of anaerobes are capable of producing RiPPs either alone or in conjunction with other secondary metabolites, such as polyketides or non-ribosomal peptides.

Conclusion: Amongst the analyzed genomes, several gene clusters encode uncharacterized RiPPs, whilst others show similarity with known RiPPs. These include a number of potential class II lanthipeptides; head-to-tail cyclized peptides and lactococcin 972-like RiPP. This study presents further evidence in support of anaerobic bacteria as an untapped natural products reservoir.

Show MeSH