Prebiotic Access To Enantioenriched Amino Acids Via Peptide-mediated Transamination Reactions

The kinetic resolution of racemic amino acids mediated by dipeptides and pyridoxal provides a prebiotically plausible route to enantioenriched proteinogenic amino acids.

The enzymatic transamination cycles that are key to modern biochemical formation of enantiopure amino acids may have evolved from this half of the reversible reaction couple. Kinetic resolution of racemic precursors emerges as a general route to enantioenrichment under prebiotic conditions.

Significance

While much progress has been made in developing prebiotically plausible synthetic chemical routes to RNA, DNA, and peptides, as well as in prebiotic metabolic pathways, the question of the emergence of biological homochirality has often been left unexplored.

Our work suggests that modern biological transamination may have evolved from a prebiotic half-reaction in reverse, effecting a kinetic resolution of racemic amino acids that preferentially leaves behind the proteinogenic amino acid enantiomer.

This reaction joins several other recently reported prebiotically plausible kinetic resolutions that have been shown to produce enantioenriched sugar and amino acid building blocks. Kinetic resolution may be seen as an effective means of imparting stereochemical control that preceded and aided the development of highly selective asymmetric biocatalysts.

Jinhan Yu, Andrea Darú, Min Deng, Donna G Blackmond
PMID: 38315856 PMCID: PMC10873602 (available on 2024-08-05) DOI: 10.1073/pnas.2315447121
Prebiotic access to enantioenriched amino acids via peptide-mediated transamination reactions, PubMed

Astrobiology