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

Related in: MedlinePlus

Lichenicidin-like lanthipeptides. A Lichenicidin biosynthetic gene cluster (lic) of B. licheniformis in comparison to putative lichenicidin gene clusters of C. botulinum H04402 065 and C. cellulovorans 743B; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Comparison of lichenicidin peptide precursors (LicA1 and LicA2) and the putative precursor peptides of C. botulinum H04402 065 (H04402_00614 and H04402_00615) and C. cellulovorans 743B (Clocel_4229 and Clocel_4226); Glycine-Glycine motif indicates the cleavage site of leader sequence and core peptide (bold) C Formation of lanthionine (lan) and methyl-lanthionine (me-lan) moieties by dehydration of serine/threonine residues to dehydroalanine (dha) / dehydrobutyrine (dhb) and subsequent cyclization with a cysteine residue catalyzed by LanM D Amino acid structure of lichenicidin α-subunit (Bliα).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Lichenicidin-like lanthipeptides. A Lichenicidin biosynthetic gene cluster (lic) of B. licheniformis in comparison to putative lichenicidin gene clusters of C. botulinum H04402 065 and C. cellulovorans 743B; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Comparison of lichenicidin peptide precursors (LicA1 and LicA2) and the putative precursor peptides of C. botulinum H04402 065 (H04402_00614 and H04402_00615) and C. cellulovorans 743B (Clocel_4229 and Clocel_4226); Glycine-Glycine motif indicates the cleavage site of leader sequence and core peptide (bold) C Formation of lanthionine (lan) and methyl-lanthionine (me-lan) moieties by dehydration of serine/threonine residues to dehydroalanine (dha) / dehydrobutyrine (dhb) and subsequent cyclization with a cysteine residue catalyzed by LanM D Amino acid structure of lichenicidin α-subunit (Bliα).

Mentions: The lanthipeptides are defined by the presence of the non-proteinogenic amino acids lanthionine and 3-methyllanthionine, which are crosslinked via a thioether linkage at their β-carbon atoms[1, 2, 5, 19, 20]. The best-known and characterized lanthipeptide is nisin, which was first reported in 1928, although its structure was only finally elucidated in the 1970s[9, 10]. The biosynthetic genes for nisin had to wait until the late 1980s to be uncovered, and since this time many lan biosynthetic loci have been identified. The synthesis of the unusual lanthionine and 3-methyllanthionine residues occurs by dehydration of serine and threonine to dehydroalanine (dha) and dehydrobutyrine (dhb), respectively, via phosphorylated intermediates, which subsequently undergo a Michael-type addition (cyclization) with a cysteine residue[1, 5, 19] (Figure 3).Figure 3


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

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

Lichenicidin-like lanthipeptides. A Lichenicidin biosynthetic gene cluster (lic) of B. licheniformis in comparison to putative lichenicidin gene clusters of C. botulinum H04402 065 and C. cellulovorans 743B; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Comparison of lichenicidin peptide precursors (LicA1 and LicA2) and the putative precursor peptides of C. botulinum H04402 065 (H04402_00614 and H04402_00615) and C. cellulovorans 743B (Clocel_4229 and Clocel_4226); Glycine-Glycine motif indicates the cleavage site of leader sequence and core peptide (bold) C Formation of lanthionine (lan) and methyl-lanthionine (me-lan) moieties by dehydration of serine/threonine residues to dehydroalanine (dha) / dehydrobutyrine (dhb) and subsequent cyclization with a cysteine residue catalyzed by LanM D Amino acid structure of lichenicidin α-subunit (Bliα).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Lichenicidin-like lanthipeptides. A Lichenicidin biosynthetic gene cluster (lic) of B. licheniformis in comparison to putative lichenicidin gene clusters of C. botulinum H04402 065 and C. cellulovorans 743B; Numbers represent the locus tag for each gene within the genome sequence of each organism. B Comparison of lichenicidin peptide precursors (LicA1 and LicA2) and the putative precursor peptides of C. botulinum H04402 065 (H04402_00614 and H04402_00615) and C. cellulovorans 743B (Clocel_4229 and Clocel_4226); Glycine-Glycine motif indicates the cleavage site of leader sequence and core peptide (bold) C Formation of lanthionine (lan) and methyl-lanthionine (me-lan) moieties by dehydration of serine/threonine residues to dehydroalanine (dha) / dehydrobutyrine (dhb) and subsequent cyclization with a cysteine residue catalyzed by LanM D Amino acid structure of lichenicidin α-subunit (Bliα).
Mentions: The lanthipeptides are defined by the presence of the non-proteinogenic amino acids lanthionine and 3-methyllanthionine, which are crosslinked via a thioether linkage at their β-carbon atoms[1, 2, 5, 19, 20]. The best-known and characterized lanthipeptide is nisin, which was first reported in 1928, although its structure was only finally elucidated in the 1970s[9, 10]. The biosynthetic genes for nisin had to wait until the late 1980s to be uncovered, and since this time many lan biosynthetic loci have been identified. The synthesis of the unusual lanthionine and 3-methyllanthionine residues occurs by dehydration of serine and threonine to dehydroalanine (dha) and dehydrobutyrine (dhb), respectively, via phosphorylated intermediates, which subsequently undergo a Michael-type addition (cyclization) with a cysteine residue[1, 5, 19] (Figure 3).Figure 3

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