Throughout the past century, natural products produced by bacteria have been a bountiful source of new pharmaceutical compounds. Recently, the rate at which new natural products are discovered has fallen into decline, in part due to the problem of rediscovery of known compounds by bioassay-guided fractionation methods. Technologies such as genomic sequencing, mass spectrometry, proteomics and bioinformatics have experienced disruptive advancements in recent years, providing a powerful toolbox well suited for the discovery and characterization of novel natural products.  By integrating these technologies, our group has developed a targeted approach to natural products discovery: proteomics investigation of secondary metabolism (PrISM). In PrISM, an organism is first subjected to proteomic analysis to identify the expression of biosynthetic enzymes such as non-ribosomal peptide synthetases, or polyketide synthetases. Peptide sequence information obtained in this way can then be mapped to a database prepared from the translated genomic sequence to indicate which natural product clusters are actually expressed. Once a cluster is identified to be expressed, bioinformatics approaches can be applied to obtain clues about the structure of the biosynthetic product. This information can then be used in a targeted discovery approach, such as stable-isotope incorporation or structure-guided bioassay.

"Omics" approach to natural product discovery in actinobacteria.

246th National Meeting (2013)

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