Biological systems are a tremendous source of chemical diversity and a unique opportunity for the discovery of novel bioactive molecules of pharmaceutical interest. However, the exploration of this chemical space has remained largely incomplete due to the lack of technologies for the fast and accurate identification and structural characterization of metabolites, and for the interrogation of their biological activity. Metabolomics, i.e., the comprehensive and unbiased analysis of metabolites and lipids in biological systems, has recently prompted a renaissance of metabolism research and now provides unprecedented tools to move forward the discovery of active metabolites at accelerated pace. Moreover, the combination of metabolomics strategies with genomics, transcriptomics, and proteomics data can unlock the interpretation of metabolite activities at systems-level. Here we discuss the utility and potential of global metabolomics and systems biology approaches coupled with functional and phenotypic activity screenings, for charting at high-throughput the activity of metabolites of pharmaceutical interest. We will further discuss the application of systems biology approaches to elucidate the mechanism of action and unravel novel druggable targets underlyig metabolite activity. Taken together, this workflow showcases the potential of high-thoughput metabolomics and systems biology for accelerating the discovery of active metabolites and novel druggable molecular targets.

Accelerating drug discovery by high throughput metabolomics and systems biology

ACS Fall 2021

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