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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 NHLP/Niff. A Structure of putative NHLP/Niff related gene clusters of D. baarsii 2st14, E. lenta VPI 0255, D. hafniense DCP-2, D. acetoxidans DSM 771, S. wolfei subsp. wolfei str. Goettingen, P. thermopropionicum SI; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Comparison of the putative precursor peptides with VAGG-motif separating the leader and core peptide in bold.
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Fig8: Detected putative NHLP/Niff. A Structure of putative NHLP/Niff related gene clusters of D. baarsii 2st14, E. lenta VPI 0255, D. hafniense DCP-2, D. acetoxidans DSM 771, S. wolfei subsp. wolfei str. Goettingen, P. thermopropionicum SI; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Comparison of the putative precursor peptides with VAGG-motif separating the leader and core peptide in bold.

Mentions: The putative anaerobic NHLP/Niff11 clusters are located exclusively in the Actinobacteria, δ-Proteobacteria and Firmicutes phyla and all putative precursor peptides are annotated as NHLP or Niff11-superfamily proteins. The leader sequences (taken as the amino acid sequence before the GG motif) have a range between 66–85 amino acids, whilst the core sequences, taken as the amino acid sequence following the conserved VAGG or VSGG motif, are quite variable in length (14–59 amino acids) (Table 7, Figure 8B). The number of putative precursor peptides also differs from one to three depending on the individual gene cluster (Figure 8A). It is striking that cyclodehydratase and dehydrogenase related genes were only observed in the gene clusters present in Syntrophomonas wolfei subsp. wolfei str. Goettingen and Pelotomaculum thermopropionicum (Figure 8A). In the other cases a transporter with an N-terminal peptidase was identified, as well as several radical SAM proteins, which may be responsible for the modification steps of the NHLP/Niff11 precursors. Furthermore, proteins important for secretion are also located within several of the gene clusters (Figure 8A).Table 7


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 NHLP/Niff. A Structure of putative NHLP/Niff related gene clusters of D. baarsii 2st14, E. lenta VPI 0255, D. hafniense DCP-2, D. acetoxidans DSM 771, S. wolfei subsp. wolfei str. Goettingen, P. thermopropionicum SI; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Comparison of the putative precursor peptides with VAGG-motif separating the leader and core peptide in bold.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig8: Detected putative NHLP/Niff. A Structure of putative NHLP/Niff related gene clusters of D. baarsii 2st14, E. lenta VPI 0255, D. hafniense DCP-2, D. acetoxidans DSM 771, S. wolfei subsp. wolfei str. Goettingen, P. thermopropionicum SI; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Comparison of the putative precursor peptides with VAGG-motif separating the leader and core peptide in bold.
Mentions: The putative anaerobic NHLP/Niff11 clusters are located exclusively in the Actinobacteria, δ-Proteobacteria and Firmicutes phyla and all putative precursor peptides are annotated as NHLP or Niff11-superfamily proteins. The leader sequences (taken as the amino acid sequence before the GG motif) have a range between 66–85 amino acids, whilst the core sequences, taken as the amino acid sequence following the conserved VAGG or VSGG motif, are quite variable in length (14–59 amino acids) (Table 7, Figure 8B). The number of putative precursor peptides also differs from one to three depending on the individual gene cluster (Figure 8A). It is striking that cyclodehydratase and dehydrogenase related genes were only observed in the gene clusters present in Syntrophomonas wolfei subsp. wolfei str. Goettingen and Pelotomaculum thermopropionicum (Figure 8A). In the other cases a transporter with an N-terminal peptidase was identified, as well as several radical SAM proteins, which may be responsible for the modification steps of the NHLP/Niff11 precursors. Furthermore, proteins important for secretion are also located within several of the gene clusters (Figure 8A).Table 7

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