Limits...
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.

Show MeSH
Potential of anaerobic bacteria for PKS/NRPS/RiPP production and distribution among different phyla. A Distribution of genes for secondary metabolite production; percentage of strains containing: no PKS/NRPS/RiPP genes (green); both PKS/NRPS and RiPP (blue); only PKS/NRPS (yellow); only RiPP (red) B Distribution of secondary metabolite containing strains according to phyla and ability for secondary metabolite production (no PKS/NRPS/RiPP genes (green); both PKS/NRPS and RiPP genes (blue); only PKS/NRPS genes (yellow); only RiPP genes (red)). Firmicutes are additionally divided into Clostridia and others.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Potential of anaerobic bacteria for PKS/NRPS/RiPP production and distribution among different phyla. A Distribution of genes for secondary metabolite production; percentage of strains containing: no PKS/NRPS/RiPP genes (green); both PKS/NRPS and RiPP (blue); only PKS/NRPS (yellow); only RiPP (red) B Distribution of secondary metabolite containing strains according to phyla and ability for secondary metabolite production (no PKS/NRPS/RiPP genes (green); both PKS/NRPS and RiPP genes (blue); only PKS/NRPS genes (yellow); only RiPP genes (red)). Firmicutes are additionally divided into Clostridia and others.

Mentions: To survey the diversity of RiPPs we have undertaken a bioinformatic investigation of 211 complete and published anaerobe genomes for the presence of RiPP genes and gene clusters. Of note is the fact that anaerobes are a potential source of RiPPs, with >25% of currently sequenced anaerobe genomes encoding at least one or more RiPP classes (Table 1). It appears as though the RiPP biosynthetic gene clusters are more likely to be found in strains that possess other secondary metabolite biosynthetic gene loci, with only 10.4% of analyzed genomes containing only RiPP-encoding genes. However, these trends may only be predictable for the phyla Firmicutes, Actinobacteria, Bacteriodetes, Proteobacteria and Spirochaetes, which comprise a sufficient number of genomes for a representative analysis (Table 1, Figure 1). To what extent the present results also represent a general trend for the other phyla is difficult to estimate and more genomes of these phyla are required. The combination of PKS/NRPS and RiPPs appears to be limited to the phyla Actinobacteria, Proteobacteria and Firmicutes, confirming previous reports in aerobic organisms[1]. Notably, RiPP biosynthetic gene clusters were not identified in any anaerobes from the phylum Bacteriodetes, although aerobes from this phylum have been shown to possess lanthipeptide gene clusters[1]. In contrast to the situation with PKS/NRPS gene clusters, which are absent in Spirochaetes genomes, a small number of these organisms appear capable of producing RiPPs (Table 1, Figure 1). As is the case with PKS/NRPS biosynthetic gene clusters, of the sequenced genomes in our analysis, the Firmicutes appear to contain the highest percentage of RiPP producers, with approximately 75% of the Clostridium species analyzed being capable of producing PKS/NRPS or RiPPs.Table 1


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

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

Potential of anaerobic bacteria for PKS/NRPS/RiPP production and distribution among different phyla. A Distribution of genes for secondary metabolite production; percentage of strains containing: no PKS/NRPS/RiPP genes (green); both PKS/NRPS and RiPP (blue); only PKS/NRPS (yellow); only RiPP (red) B Distribution of secondary metabolite containing strains according to phyla and ability for secondary metabolite production (no PKS/NRPS/RiPP genes (green); both PKS/NRPS and RiPP genes (blue); only PKS/NRPS genes (yellow); only RiPP genes (red)). Firmicutes are additionally divided into Clostridia and others.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Potential of anaerobic bacteria for PKS/NRPS/RiPP production and distribution among different phyla. A Distribution of genes for secondary metabolite production; percentage of strains containing: no PKS/NRPS/RiPP genes (green); both PKS/NRPS and RiPP (blue); only PKS/NRPS (yellow); only RiPP (red) B Distribution of secondary metabolite containing strains according to phyla and ability for secondary metabolite production (no PKS/NRPS/RiPP genes (green); both PKS/NRPS and RiPP genes (blue); only PKS/NRPS genes (yellow); only RiPP genes (red)). Firmicutes are additionally divided into Clostridia and others.
Mentions: To survey the diversity of RiPPs we have undertaken a bioinformatic investigation of 211 complete and published anaerobe genomes for the presence of RiPP genes and gene clusters. Of note is the fact that anaerobes are a potential source of RiPPs, with >25% of currently sequenced anaerobe genomes encoding at least one or more RiPP classes (Table 1). It appears as though the RiPP biosynthetic gene clusters are more likely to be found in strains that possess other secondary metabolite biosynthetic gene loci, with only 10.4% of analyzed genomes containing only RiPP-encoding genes. However, these trends may only be predictable for the phyla Firmicutes, Actinobacteria, Bacteriodetes, Proteobacteria and Spirochaetes, which comprise a sufficient number of genomes for a representative analysis (Table 1, Figure 1). To what extent the present results also represent a general trend for the other phyla is difficult to estimate and more genomes of these phyla are required. The combination of PKS/NRPS and RiPPs appears to be limited to the phyla Actinobacteria, Proteobacteria and Firmicutes, confirming previous reports in aerobic organisms[1]. Notably, RiPP biosynthetic gene clusters were not identified in any anaerobes from the phylum Bacteriodetes, although aerobes from this phylum have been shown to possess lanthipeptide gene clusters[1]. In contrast to the situation with PKS/NRPS gene clusters, which are absent in Spirochaetes genomes, a small number of these organisms appear capable of producing RiPPs (Table 1, Figure 1). As is the case with PKS/NRPS biosynthetic gene clusters, of the sequenced genomes in our analysis, the Firmicutes appear to contain the highest percentage of RiPP producers, with approximately 75% of the Clostridium species analyzed being capable of producing PKS/NRPS or RiPPs.Table 1

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