Cited by 103Origins and Evolution of LifeRNA and protein synthesis mechanismsChemical Reaction Mechanisms

A prebiotic basis for ATP as the universal energy currency

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Pinna, Silvana, Kunz, Cäcilia, Halpern, Aaron, Harrison, Stuart A., Jordan, Sean F., Ward, John, Werner, Finn, Lane, Nick·2022·PLOS Biology

Abstract

ATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires 6 phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleoside triphosphates, remains a mystery. Here, we show that the deep conservation of ATP might reflect its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate (AcP), which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. We confirm earlier results showing that AcP can phosphorylate ADP to ATP at nearly 20% yield in water in the presence of Fe 3+ ions. We then show that Fe 3+ and AcP are surprisingly favoured. A wide range of prebiotically relevant ions and minerals failed to catalyse ADP phosphorylation. From a panel of prebiotic phosphorylating agents, only AcP, and to a lesser extent carbamoyl phosphate, showed any significant phosphorylating potential. Critically, AcP did not phosphorylate any other nucleoside diphosphate. We use these data, reaction kinetics, and molecular dynamic simulations to infer a possible mechanism. Our findings might suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions.

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  1. [1]Nicholls DG, Ferguson S. Bioenergetics. 4th edition. Academic Press; 2013.

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Authors
Pinna, S., Kunz, C., Halpern, A., Harrison, S. A., Jordan, S. F., Ward, J., Werner, F., & Lane, N.
Affiliations
  • University College London (GB)
  • Institute of Structural and Molecular Biology (GB)
Corresponding author
Lane, Nick
Venue
PLOS Biology
Published
2022-10-04
Volume
20
Issue
10
Pages
e3001437
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
OpenAlex
W4301374198
Cited by
103
References
151
Citations by year
2026: 29 · 2025: 17 · 2024: 33 · 2023: 22 · 2022: 2
FWCI
7.40
Type
journal article
Language
en
Open access
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Biotechnology and Biological Sciences Research Council (BB/V003542/1)
  • bgc3
  • Natural Environment Research Council (2236041)
Topics
  • Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Physical Sciences › Chemistry › Organic Chemistry › Chemical Reaction Mechanisms
Keywords
prebiotic chemistry, acetyl phosphate, ADP phosphorylation, nucleoside triphosphates, purine biosynthesis, protometabolism, iron catalysis, substrate-level phosphorylation, carbamoyl phosphate, molecular dynamics simulation
MeSH terms
Acetyl Coenzyme A, Adenosine Diphosphate, Adenosine Triphosphate, Carbamyl Phosphate, Kinetics, Nucleosides, Organophosphates, Diphosphates, Water

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