Metabolite discovery: Biochemistry’s scientific driver

Metabolite identification represents a major challenge, and opportunity, for biochemistry. The collective characterization and quantification of metabolites in living organisms, with its many successes, represents a major biochemical knowledgebase and the foundation of metabolism's rebirth in the 21st century; yet, characterizing newly observed metabolites has been an enduring obstacle. Crystallography and NMR spectroscopy have been of extraordinary importance, although their applicability in resolving metabolism's fine structure has been restricted by their intrinsic requirement of sufficient and sufficiently pure materials. Mass spectrometry has been a key technology, especially when coupled with high-performance separation technologies and emerging informatic and database solutions. Even more so, the collective of artificial intelligence technologies are rapidly evolving to help solve the metabolite characterization conundrum. This perspective describes this challenge, how it was historically addressed, and how metabolomics is evolving to address it today and in the future.