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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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Related in: MedlinePlus

Detected putative lactococcins like RiPPs. A Lactococcin 972 gene cluster (lcl) of L. lactis subsp. lactis in comparison to detected putative lactococcin 972 like gene clusters in D. hafniense Y51, B. longuminfantis JCM 1222 and P. acnes KPA171202; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Lactococcin A gene cluster (lcn) of L. lactis subsp. cremoris and detected putative lactococcin A-like gene cluster in C. perfringens SM 101; (T = transposase); Numbers represent the locus tag for each gene within the genome sequence of each organism.
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Fig10: Detected putative lactococcins like RiPPs. A Lactococcin 972 gene cluster (lcl) of L. lactis subsp. lactis in comparison to detected putative lactococcin 972 like gene clusters in D. hafniense Y51, B. longuminfantis JCM 1222 and P. acnes KPA171202; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Lactococcin A gene cluster (lcn) of L. lactis subsp. cremoris and detected putative lactococcin A-like gene cluster in C. perfringens SM 101; (T = transposase); Numbers represent the locus tag for each gene within the genome sequence of each organism.

Mentions: Like many other RiPPs, lactococcins possess an N-terminal leader sequence, which terminates in a glycine-glycine motif. This motif is an important signal unit for the respective transporters which secrete the substance and simultaneously cleave off the leader sequence[75]. Lactococcin 972 is homodimeric RiPP, which is only encoded by one structural gene[76]. This gene encodes a 91 amino acid precursor peptide of which 25 amino acids comprise the leader sequence and the remainder, the core sequence[76, 77]. In addition to the precursor peptide named LclA the gene cluster encodes a transporter (LclB) and an additional protein that is important for immunity (Figure 10A). Lactococcin 972 blocks the incorporation of lipid II, an essential cell wall building block[77–79].Figure 10


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 lactococcins like RiPPs. A Lactococcin 972 gene cluster (lcl) of L. lactis subsp. lactis in comparison to detected putative lactococcin 972 like gene clusters in D. hafniense Y51, B. longuminfantis JCM 1222 and P. acnes KPA171202; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Lactococcin A gene cluster (lcn) of L. lactis subsp. cremoris and detected putative lactococcin A-like gene cluster in C. perfringens SM 101; (T = transposase); Numbers represent the locus tag for each gene within the genome sequence of each organism.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig10: Detected putative lactococcins like RiPPs. A Lactococcin 972 gene cluster (lcl) of L. lactis subsp. lactis in comparison to detected putative lactococcin 972 like gene clusters in D. hafniense Y51, B. longuminfantis JCM 1222 and P. acnes KPA171202; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Lactococcin A gene cluster (lcn) of L. lactis subsp. cremoris and detected putative lactococcin A-like gene cluster in C. perfringens SM 101; (T = transposase); Numbers represent the locus tag for each gene within the genome sequence of each organism.
Mentions: Like many other RiPPs, lactococcins possess an N-terminal leader sequence, which terminates in a glycine-glycine motif. This motif is an important signal unit for the respective transporters which secrete the substance and simultaneously cleave off the leader sequence[75]. Lactococcin 972 is homodimeric RiPP, which is only encoded by one structural gene[76]. This gene encodes a 91 amino acid precursor peptide of which 25 amino acids comprise the leader sequence and the remainder, the core sequence[76, 77]. In addition to the precursor peptide named LclA the gene cluster encodes a transporter (LclB) and an additional protein that is important for immunity (Figure 10A). Lactococcin 972 blocks the incorporation of lipid II, an essential cell wall building block[77–79].Figure 10

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
Related in: MedlinePlus