Jun 8, 2015

Phylogenomic analysis of natural products biosynthetic gene clusters allows discovery of arseno-organic metabolites in model streptomycetes

BioRxiv : the Preprint Server for Biology
Pablo Cruz-MoralesFrancisco Barona-Gomez

Abstract

Natural products from microbes have provided humans with beneficial antibiotics for millennia. However, a decline in the pace of antibiotic discovery exerts pressure on human health as antibiotic resistance spreads, a challenge that may better faced by unveiling chemical diversity produced by microbes. Current microbial genome mining approaches have revitalized research into antibiotics, but the empirical nature of these methods limits the chemical space that is explored. Here, we address the problem of finding novel pathways by incorporating evolutionary principles into genome mining. We recapitulated the evolutionary history of twenty-three enzyme families previously uninvestigated in the context of natural product biosynthesis in Actinobacteria, the most proficient producers of natural products. Our genome evolutionary analyses where based on the assumption that expanded -repurposed enzyme families- from central metabolism, occur frequently and thus have the potential to catalyze new conversions in the context of natural products biosynthesis. Our analyses led to the discovery of biosynthetic gene clusters coding for hidden chemical diversity, as validated by comparing our predictions with those from state-of-the-art genome ...Continue Reading

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Mentioned in this Paper

Metabolic Process, Cellular
Biochemical Pathway
Research
Exertion
Complement System Proteins
Light-driven Proton Transport
Genome
Enzymes, antithrombotic
Streptomyces coelicolor
Antibiotic throat preparations

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