Abstract
BackgroundCyanobacteria are an ancient lineage of photosynthetic bacteria from which hundreds of natural products have been described, including many notorious toxins but also potent natural products of interest to the pharmaceutical and biotechnological industries. Many of these compounds are the products of non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) pathways. However, current understanding of the diversification of these pathways is largely based on the chemical structure of the bioactive compounds, while the evolutionary forces driving their remarkable chemical diversity are poorly understood.ResultsWe carried out a phylum-wide investigation of genetic diversification of the cyanobacterial NRPS and PKS pathways for the production of bioactive compounds. 452 NRPS and PKS gene clusters were identified from 89 cyanobacterial genomes, revealing a clear burst in late-branching lineages. Our genomic analysis further grouped the clusters into 286 highly diversified cluster families (CF) of pathways. Some CFs appeared vertically inherited, while others presented a more complex evolutionary history. Only a few horizontal gene transfers were evidenced amongst strongly conserved CFs in the phylum, while several others have undergone drastic gene shuffling events, which could result in the observed diversification of the pathways.ConclusionsTherefore, in addition to toxin production, several NRPS and PKS gene clusters are devoted to important cellular processes of these bacteria such as nitrogen fixation and iron uptake. The majority of the biosynthetic clusters identified here have unknown end products, highlighting the power of genome mining for the discovery of new natural products.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-977) contains supplementary material, which is available to authorized users.
Highlights
Cyanobacteria are an ancient lineage of photosynthetic bacteria from which hundreds of natural products have been described, including many notorious toxins and potent natural products of interest to the pharmaceutical and biotechnological industries
Conclusions: in addition to toxin production, several non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) gene clusters are devoted to important cellular processes of these bacteria such as nitrogen fixation and iron uptake
Identification of NRPS/PKS pathways Genomic analysis identified 452 biosynthetic gene clusters including 190 NRPS, 162 PKS, and 100 hybrid gene clusters encoding both NRPS and PKS enzymes from 89 cyanobacteria out of the 126 genomes of the CyanoGEBA dataset covering the diversity of the phylum [1] (Table 1)
Summary
Cyanobacteria are an ancient lineage of photosynthetic bacteria from which hundreds of natural products have been described, including many notorious toxins and potent natural products of interest to the pharmaceutical and biotechnological industries Many of these compounds are the products of non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) pathways. In a recent effort of better representing the cyanobacterial phylum at the genomic level, we initiated the genetic potential for the secondary metabolite production in Cyanobacteria [1] This preliminary study confirmed the impressive potential for natural product production across the entire cyanobacterial lineage as 70% of the cyanobacterial genomes contained the polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) pathways or hybrids thereof. Cyanobacteria dedicated about 5% of their genomes for these pathways, with an average of five NRPS/PKS clusters per genome [1]
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