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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 lasso peptides. A Microcin J25 (mcj) (E. coli) and Lariatin (lar) (R. jostii K01-B0171) gene clusters in comparision to putative lasso peptide gene clusters of G. uraniireducens Rf4, P. propionicus DSM 2379, D. acetoxidans DSM 11069 (* = precursor peptide identified in this study, # = precursor peptide identified by[71]), B. proteoclasticum B313, D. acetoxidans DSM 771, S. glycolicus DSM 8271 and C. perfringens str. 13; Annotation of the putative precursor peptide was not conclusively possible in most cases; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Cleavage of the lariatin precursor peptide by a putative protease (LarD); Isopeptide bond (green) formation by LarB between the N-terminal amino acid glycine (red) and a glutamate (red) leads to the formation of a 8- membered macrolactame ring in lariatin. C Lasso peptide structure of lariatin (isopeptide bond (green)).
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Fig9: Detected putative lasso peptides. A Microcin J25 (mcj) (E. coli) and Lariatin (lar) (R. jostii K01-B0171) gene clusters in comparision to putative lasso peptide gene clusters of G. uraniireducens Rf4, P. propionicus DSM 2379, D. acetoxidans DSM 11069 (* = precursor peptide identified in this study, # = precursor peptide identified by[71]), B. proteoclasticum B313, D. acetoxidans DSM 771, S. glycolicus DSM 8271 and C. perfringens str. 13; Annotation of the putative precursor peptide was not conclusively possible in most cases; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Cleavage of the lariatin precursor peptide by a putative protease (LarD); Isopeptide bond (green) formation by LarB between the N-terminal amino acid glycine (red) and a glutamate (red) leads to the formation of a 8- membered macrolactame ring in lariatin. C Lasso peptide structure of lariatin (isopeptide bond (green)).

Mentions: Lasso peptides are among the most extraordinary RiPPs, and their rigid structure gives them enormous stability against heat, chemical attack and proteases[1, 56, 57]. So named because of their particular knotted structure, the lasso peptides are usually 16–23 amino acids in length and contain an 8–9 membered macrolactam ring, which is formed between the N-terminal amino group and the carboxylate of a conserved aspartate or glutamate residue at position 8 or 9, by a putative asparagine synthase like enzyme, resulting in a C-terminal loop and tail formation[1, 56, 57] (Figure 9B & C). Three subgroups of the lasso peptides have been characterized. The prototypical members of the group I lasso peptides include siamycin I[58], siamycin II[58] and RP71955[59], all of which possess two disulfide bonds and an N-terminal cysteine[1, 56, 57]. In contrast, group II lasso peptides contain no disulfide bonds, and the N-terminal amino acid is glycine[1, 56, 57], with examples in the form of microcin J25[60, 61], lariatin[62] and capistruin[63, 64]. Lasso peptide BI-32169[65, 66] is the only member of group III, having one disulfide bridge and glycine as the N-terminal amino acid[1, 56, 57].


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 lasso peptides. A Microcin J25 (mcj) (E. coli) and Lariatin (lar) (R. jostii K01-B0171) gene clusters in comparision to putative lasso peptide gene clusters of G. uraniireducens Rf4, P. propionicus DSM 2379, D. acetoxidans DSM 11069 (* = precursor peptide identified in this study, # = precursor peptide identified by[71]), B. proteoclasticum B313, D. acetoxidans DSM 771, S. glycolicus DSM 8271 and C. perfringens str. 13; Annotation of the putative precursor peptide was not conclusively possible in most cases; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Cleavage of the lariatin precursor peptide by a putative protease (LarD); Isopeptide bond (green) formation by LarB between the N-terminal amino acid glycine (red) and a glutamate (red) leads to the formation of a 8- membered macrolactame ring in lariatin. C Lasso peptide structure of lariatin (isopeptide bond (green)).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig9: Detected putative lasso peptides. A Microcin J25 (mcj) (E. coli) and Lariatin (lar) (R. jostii K01-B0171) gene clusters in comparision to putative lasso peptide gene clusters of G. uraniireducens Rf4, P. propionicus DSM 2379, D. acetoxidans DSM 11069 (* = precursor peptide identified in this study, # = precursor peptide identified by[71]), B. proteoclasticum B313, D. acetoxidans DSM 771, S. glycolicus DSM 8271 and C. perfringens str. 13; Annotation of the putative precursor peptide was not conclusively possible in most cases; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Cleavage of the lariatin precursor peptide by a putative protease (LarD); Isopeptide bond (green) formation by LarB between the N-terminal amino acid glycine (red) and a glutamate (red) leads to the formation of a 8- membered macrolactame ring in lariatin. C Lasso peptide structure of lariatin (isopeptide bond (green)).
Mentions: Lasso peptides are among the most extraordinary RiPPs, and their rigid structure gives them enormous stability against heat, chemical attack and proteases[1, 56, 57]. So named because of their particular knotted structure, the lasso peptides are usually 16–23 amino acids in length and contain an 8–9 membered macrolactam ring, which is formed between the N-terminal amino group and the carboxylate of a conserved aspartate or glutamate residue at position 8 or 9, by a putative asparagine synthase like enzyme, resulting in a C-terminal loop and tail formation[1, 56, 57] (Figure 9B & C). Three subgroups of the lasso peptides have been characterized. The prototypical members of the group I lasso peptides include siamycin I[58], siamycin II[58] and RP71955[59], all of which possess two disulfide bonds and an N-terminal cysteine[1, 56, 57]. In contrast, group II lasso peptides contain no disulfide bonds, and the N-terminal amino acid is glycine[1, 56, 57], with examples in the form of microcin J25[60, 61], lariatin[62] and capistruin[63, 64]. Lasso peptide BI-32169[65, 66] is the only member of group III, having one disulfide bridge and glycine as the N-terminal amino acid[1, 56, 57].

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