Systematic mapping of protein–metabolite interactions with mass spectrometry-based techniques

The recent rapid advance of systematic mapping of protein–metabolite interactions (PMIs) in both prokaryotic and eukaryotic cells has been catalyzed by development of innovative and effective proteomics or metabolomics strategies all based on large-scale mass spectrometry (MS) analysis of biomolecules. Both metabolite-centric and protein-centric approaches have been established to profile PMIs in the native cellular matrix treated by specific metabolites or proteins. Here we will review the development and application of versatile MS-based proteomics and metabolomics techniques for global PMI mapping in different species, which lead to the discovery of numerous uncharacterized PMIs that may reveal new interaction-derived functionality. We further discuss the strengths and limitations of different PMI mapping approaches as well as the key elements in MS quantification and data mining for reliable PMI identification.