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Updated: Aug 7, 2025

Metabolic Pathway Confirmation and Discovery Through 13C-labeling of Proteinogenic Amino Acids
Published on: January 26, 2012
Thermally Accessible Prebiotic Pathways for Forming Ribonucleic Acid and Protein Precursors from Aqueous Hydrogen
Qiyuan Zhao1, Sanjay S Garimella1, Brett M Savoie1
1Davidson School of Chemical Engineering, Purdue University, West Lafayette, Indiana 47906, United States.
Abstract:
The search for prebiotic chemical pathways to biologically relevant molecules is a long-standing puzzle that has generated a menagerie of competing hypotheses with limited experimental prospects for falsification. However, the advent of computational network exploration methodologies has created the opportunity to compare the kinetic plausibility of various channels and even propose new pathways. Here, the space of organic molecules that can be formed within four polar or pericyclic reactions from water and hydrogen cyanide (HCN), two established prebiotic candidates for generating biological precursors, was comprehensively explored with a state-of-the-art exploration algorithm. A surprisingly diverse reactivity landscape was revealed within just a few steps of these simple molecules. Reaction pathways to several biologically relevant molecules were discovered involving lower activation energies and fewer reaction steps compared with recently proposed alternatives. Accounting for water-catalyzed reactions qualitatively affects the interpretation of the network kinetics. The case-study also highlights omissions of simpler and lower barrier reaction pathways to certain products by other algorithms that qualitatively affect the interpretation of HCN reactivity.
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