Metabolite Functions Revealed by Mass Spectrometry-Based Target Engagement Proteomics Approaches

In addition to their roles in energetics and biosynthesis, endogenous metabolites have functional roles performed in part through protein interactions that result in allosteric regulation, transcriptional regulation, and post-translational modifications. Novel bioactive roles for metabolites continue to emerge in cancer progression, immune response, and host–pathogen interactions. Defining metabolite-protein interactions will further reveal bioactive metabolite downstream effects and help to characterize the intersection between the metabolome and the proteome. Here, we summarize recently revealed secondary functions for metabolites that have been uncovered by mass spectrometry-based approaches for small molecule target engagement. We propose that further developments and application of these approaches will greatly advance our understanding of metabolite functions and may facilitate large-scale metabolome-proteome interaction networks that harbor new targets for diseases such as cancer.