A framework for understanding post-translational modifications of metabolic origin.

Metabolites, beyond their canonical roles in energy production and biosynthesis, also serve as precursors for a diverse array of post-translational modifications (PTMs). The functional significance of PTMs in physiology and disease has attracted increasing attention, and the landscape of metabolite-mediated PTMs has expanded markedly in recent years. In this review, we summarize recently identified metabolite-mediated PTMs categorized by their diverse metabolic origins, along with their proteomic discoveries, regulations, and functions. We further highlight the utility of chemical proteomics in uncovering previously unrecognized PTMs and discuss current challenges in studying PTMs. Together, these advances enhance our understanding of the connection between metabolism and PTMs.