Delve into the intriguing world of prebiotic chemistry with Dr. Krishnamurthy as we explore the origins of α-amino acids and the evolutionary shift from the Strecker reaction to modern biological pathways. We discuss how α-ketoacids, through the Bucherer–Bergs pathway, react with cyanide and ammonia to form corresponding α-amino acids, highlighting the prebiotic transformation of oxaloacetate to aspartate. This transformation enables the formation of dihydroorotate, mirroring the biochemical synthesis of orotate—a precursor to pyrimidine nucleobases. We also examine how glyoxylate forms both glycine and orotate and reacts with malonate and urea to produce aspartate and dihydroorotate. Our conversation extends to the previously demonstrated protometabolic analogues of the Krebs cycle, underscoring the possibility of a natural emergence of biological pathways from prebiotic chemistry. This insightful discussion with Dr. Krishnamurthy illuminates the seamless transition from the primordial world of chemistry to the complexity of contemporary metabolism.

Key Words: Prebiotic Chemistry, α-Amino Acids, Strecker Reaction, Bucherer–Bergs Pathway, α-Ketoacids, Oxaloacetate, Aspartate, Dihydroorotate, Orotate, Pyrimidine Nucleobases, Glyoxylate, Glycine, Malonate, Urea, Protometabolic Analogues, Krebs Cycle, Metabolic Evolution.

Pulletikurti et al. Prebiotic synthesis of α-amino acids and orotate from α-ketoacids potentiates transition to extant metabolic pathways. Nat. Chem. (2022). https://doi.org/10.1038/s41557-022-00999-w