From Amino Acids to α‐Keto Acids via β‐Elimination and Transamination Initiates a Pathway to Prebiotic Reaction Networks

Abstract α‐Keto acids, such as pyruvate and glyoxylate, may have been critical in generating reaction networks at the origins of life due to their facile carbon–carbon bond formation and their hydrolytic stability. However, demonstrated prebiotic sources of these small α‐keto acids have been limited by conditions required for their production, which are not conducive for subsequent incorporation or transition into (proto)metabolic pathways. Here, we demonstrate an abiotic generation of α‐keto acids from only two amino acids, starting with the phosphorylation and dehydration of serine (Ser) coupled with a transamination with glycine (Gly), to produce both pyruvate and glyoxylate. This triggers an in situ reaction pathway producing higher‐order α‐keto acids, including amino acid precursors found in modern biology. These findings may help elucidate how protometabolic chemical networks can emerge on the early Earth under mild aqueous conditions, leading to a coupled amino acid—α‐keto acid chemical system capable of supporting a more robust metabolism.