Prebiotic Synthesis of α-Amino Acids and Orotate from α-Ketoacids Potentiates Transition to Extant Metabolic Pathways

Abstract

The Strecker reaction of aldehydes is the preeminent pathway to explain the prebiotic origins of a-amino acids. However, biology employs transamination of a-ketoacids to give rise to amino acids which are then transformed to nucleobases, implying subsequent evolution of the biosynthetic pathways – abiotically or biotically. Herein, we show that a-ketoacids react with cyanide and ammonia sources to form the corresponding a-amino acids – via the Bucherer-Bergs pathway. An efficient prebiotic transformation of oxaloacetate to aspartate via N-carbamoyl aspartate enables the simultaneous formation of dihydroorotate, paralleling the biochemical synthesis of orotate as the precursor to pyrimidine nucleobases. Glyoxylate forms both glycine and orotate, and reacts with malonate and urea to form aspartate and dihydroorotate. These results, along with the previously demonstrated protometabolic analogs of the Krebs cycle suggest that there can be a natural emergence of congruent forerunners of biological pathways with the potential for seamless transition from prebiotic chemistry to modern metabolism.

Chirality in Organic and Mineral Systems: A Review of Reactivity and Alteration Processes Relevant to Prebiotic Chemistry and Life Detection Missions

“…Another mechanism for synthesizing amino acids is through Strecker synthesis [75,[430][431][432][433]. Strecker synthesis is a two-step process that, similar to reductive amination, begins with a carbonyl species, such as an aldehyde or a ketone.…”

“…Relevant to prebiotic chemistry, the Strecker synthesis can also be mediated by ribose [438] to access selective amino acid synthesis. [75,[430][431][432][433]. Strecker synthesis is a two-step process that, similar to reductive amination, begins with a carbonyl species, such as an aldehyde or a ketone.…”