Primitive purine biosynthesis connects ancient geochemistry to modern metabolism

Abstract

A major unresolved question in the origin of life is whether there exists a continuous path from geochemical precursors to the majority of molecules in the biosphere, due in part to the autocatalytic nature of metabolic networks in modern-day organisms and high rates of extinction throughout Earth's history. Here we simulated the emergence of ancient metabolic networks to identify a feasible path from simple geochemical precursors (e.g., phosphate, sulfide, ammonia, simple carboxylic acids, and metals) to contemporary biochemistry, using only known biochemical reactions and models of primitive coenzymes. We find that purine synthesis constitutes a bottleneck for metabolic expansion, and that non-autocatalytic phosphoryl coupling agents are sufficient to enable expansion from geochemistry to modern metabolic networks. Our model predicts distinct phases of metabolic evolution, characterized by the sequential emergence of key molecules (carboxylic acids, amino acids, sugars), purines/nucleotide cofactors (ATP, NAD+), flavins, and quinones, respectively. Early phases in the resulting expansion are associated with enzymes that are metal-dependent and structurally symmetric, consistent with models of early biochemical evolution. The production of quinones in the last phase of metabolic expansion permits oxygenic photosynthesis and the production of O2, leading to a >30% increase in biomolecules. These results reveal a feasible trajectory from simple geochemical precursors to the vast majority of core biochemistry.

Prebiotic Synthesis of Aspartate Using Life’s Metabolism as a Guide

“…By extension, purine-derived species, e.g., thiamine-pyrophosphate, histidine, flavins, pterins and folates, are all linked to aspartate metabolism. It is also required across all prokaryotic metabolisms for the synthesis of nicotinamide mononucleotide (NMN) [45][46][47][48], one of the most important cofactors in most origins of life contexts [8,49].…”

Self-generating autocatalytic networks: structural results, algorithms and their relevance to early biochemistry

“…At the same time, this result also reveals that there must exist unknown prebiotic routes (or unknown non-enzymatic catalysts) to the production of organic cofactors which need to be investigated in the laboratory. For example, there are no routes in this network to produce organic cofactors such as NAD [ 12 ] and the search for the prebiotic route for its synthesis is the subject of active investigation [ 46 , 47 ]. The dependence of life on its environment is deeply rooted in its geochemical origins, as demonstrated here by the structure of biochemical autocatalysis.…”

Self-generating autocatalytic networks: structural results, algorithms, and their relevance to evolutionary processes

“…At the same time, this result reveals that there are unknown prebiotic routes (or unknown non-enzymatic catalysts) to the production of organic cofactors which must be investigated in the laboratory. For example, there are no routes in this network for the production of organic cofactors as NAD [47] and the investigation of the prebiotic route for its synthesis is subject of active investigation [12, 34].…”