The undiscovered natural product potential of Actinomycetes

Abstract

Actinomycetes have been a cornerstone species for the discovery of bioactive natural products with applications in pharmacotherapy and biotechnology. To expand the experimental evidence of their biosynthetic potential, we collected liquid-chromatography mass spectrometry untargeted metabolomics data on 948 microbial strains, mostly from Actinomycetes. This resulted in nearly two million MS/MS spectra, with an annotation rate of 13.3% corresponding to 2352 annotated molecules. Despite the efforts to link biosynthetic gene clusters to known molecules, most remain uncharacterized. This highlights the need for metabolomic data to bridge the gap between genomic potential and metabolite production. Although many unannotated spectra might correspond to different ion forms of the same molecule, the large amount of unknown molecules present in these datasets indicates that a significant number of natural products remain to be discovered, even within one of the most thoroughly studied sets of organisms. We provide a large metabolomics dataset as a public resource for data mining of microbial molecules and highlight its value by demonstrating the detection of edapochelins, recently discovered non-ribosomal peptides.