It has long been assumed that biological metabolism must have been an invention of life since its many reactions are catalyzed by enzymes, complex proteins that did not exist at life’s origins. However, my group and others have recently discovered that transition metals alone can mediate reactions of life’s most central metabolic pathways in the absence of enzymes (Wood-Ljungdahl pathway, glycolysis, parts of the Krebs cycle and reverse Krebs cycle, etc.). In contrast to ideas about the origin of life that focus only on genetics, this realization brings experimental support to a radically different vision in which biological metabolism arose from geochemical reaction networks, before enzymes or life itself, and created the molecules of genetics in the process. This proposal aims to find out how much of core biological metabolism might have emerged without enzymes and whether it could have given rise to genetics. I propose an experimental research program to identify conditions that would trigger the spontaneous emergence of metal-catalyzed versions of the biosynthetic pathways for sugar, amino acid and ribonucleotide synthesis. In contrast to approaches to prebiotic chemistry that need human intervention to direct their outcome and whose chemistries are very different from those used by life, this approach will aim, as much as is possible, for one-pot chemistry that is deeply rooted in metabolism. This tactic will ensure that what is discovered is likely to be relevant to life’s origins and even predictive about the way life operates today. This metabolism-guided approach to prebiotic chemistry will furnish deep understanding of how and why life’s biochemistry emerged and explain why it operates the way that it does today, rooted in fundamental principles of catalysis and organic chemistry.