A Caltech Library Service

Continuity between ancient geochemistry and modern metabolism enabled by non-autocatalytic purine biosynthesis

Goldford, Joshua E. and Smith, Harrison B. and Longo, Liam M. and Wing, Boswell A. and McGlynn, Shawn E. (2022) Continuity between ancient geochemistry and modern metabolism enabled by non-autocatalytic purine biosynthesis. . (Unpublished)

[img] PDF - Submitted Version
Creative Commons Attribution Non-commercial No Derivatives.

[img] PDF - Supplemental Material
Creative Commons Attribution Non-commercial No Derivatives.

[img] MS Excel (Supplemental Tables) - Supplemental Material
Creative Commons Attribution Non-commercial No Derivatives.


Use this Persistent URL to link to this item:


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.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Goldford, Joshua E.0000-0001-7315-8018
Smith, Harrison B.0000-0001-8806-9659
McGlynn, Shawn E.0000-0002-8199-7011
Alternate Title:Non-autocatalytic purine biosynthesis is required for the emergence of ancient metabolism
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. The authors thank Woodward Fisher, Avi Flamholz, and Joan Valentine for valuable discussions. J.E.G. is supported by the Gordon and Betty Moore Foundation as Physics of Living Systems Fellows through grant number GBMF4513. S.E.M. acknowledges support by NSF (Award No. 1724300) “Collaborative Research: Biochemical, Genetic, Metabolic, and Isotopic Constraints on an Ancient Thiobiosphere” and JSPS KAKENHI (Grant Numbers. JP18H01325 and 22H01343). H.B.S acknowledges support from JSPS KAKENHI Grant No. JP19K23459. Contributions. All authors designed the research. J.E.G, H.B.S. and L.M.L. prepared data. J.E.G. and H.B.S. wrote code and ran simulations. J.E.G. performed analysis. J.E.G., H.B.S. and L.M.L wrote the manuscript. All authors read and approved the final manuscript. The authors have declared no competing interest.
Funding AgencyGrant Number
Gordon and Betty Moore FoundationGBMF4513
Japan Society for the Promotion of Science (JSPS)JP18H01325
Japan Society for the Promotion of Science (JSPS)22H01343
Japan Society for the Promotion of Science (JSPS)JP19K23459
Record Number:CaltechAUTHORS:20230322-101667000.22
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:120315
Deposited By: George Porter
Deposited On:22 Mar 2023 17:28
Last Modified:22 Mar 2023 17:28

Repository Staff Only: item control page