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

Anne-Catrin Letzel,Christian Hertweck,Sacha J Pidot

doi:10.1186/1471-2164-15-983

Abstract

BackgroundRibosomally 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.ResultsWe 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.ConclusionAmongst 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-983) contains supplementary material, which is available to authorized users.

Highlights

Synthesized and post-translationally modified peptides (RiPPs) are a diverse group of biologically active bacterial molecules
In contrast to the situation with polyketide synthase (PKS)/non-ribosomal peptide synthetase (NRPS) gene clusters, which are absent in Spirochaetes genomes, a small number of these organisms appear capable of producing Ribosomally synthesized and post-translationally modified peptides (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

Summary

Introduction

Synthesized and post-translationally modified peptides (RiPPs) are a diverse group of biologically active bacterial molecules. An extensive investigation of 211 genomes of anaerobic bacteria for the presence of polyketide synthase (PKS) or non-ribosomal peptide synthetase (NRPS) encoding genes revealed a much larger potential than previously suspected and many of these PKS or NRPS loci appeared to be novel, with limited homology to previously characterized gene clusters [8] It showed that certain genera have a predisposition towards increased secondary metabolite potential (such as members of the phyla Proteobacteria and Firmicutes) and that the natural habitat of the organisms seems to play an important role – isolates from environmental strains (soil, mud) often contain up to three times more genes for secondary metabolite biosynthesis than all other habitats combined. The clostridia were shown to be a potential treasure trove of novel secondary metabolites, which the isolation of the novel antibiotics closthioamide and clostrubin have recently confirmed [13,14]

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