Article

Prebiotic synthesis of phosphoenol pyruvate by α-phosphorylation-controlled triose glycolysis

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Abstract

Phosphoenol pyruvate is the highest-energy phosphate found in living organisms and is one of the most versatile molecules in metabolism. Consequently, it is an essential intermediate in a wide variety of biochemical pathways, including carbon fixation, the shikimate pathway, substrate-level phosphorylation, gluconeogenesis and glycolysis. Triose glycolysis (generation of ATP from glyceraldehyde 3-phosphate via phosphoenol pyruvate) is among the most central and highly conserved pathways in metabolism. Here, we demonstrate the efficient and robust synthesis of phosphoenol pyruvate from prebiotic nucleotide precursors, glycolaldehyde and glyceraldehyde. Furthermore, phosphoenol pyruvate is derived within an α-phosphorylation controlled reaction network that gives access to glyceric acid 2-phosphate, glyceric acid 3-phosphate, phosphoserine and pyruvate. Our results demonstrate that the key components of a core metabolic pathway central to energy transduction and amino acid, sugar, nucleotide and lipid biosyntheses can be reconstituted in high yield under mild, prebiotically plausible conditions.

  • Compound

    phosphoenol pyruvate

  • Compound

    glycolaldehyde

  • Compound

    glycolaldehyde-2-phosphate

  • Compound

    glyceraldehyde

  • Compound

    glyceraldehyde-3-phosphate

  • Compound

    phosphoserine

  • Compound

    glyceric acid 3-phosphate

  • Compound

    glyceric acid 2-phosphate

  • Compound

    glyceric acid

  • Compound

    glyceraldehyde-2-phosphate

  • Compound

    pyruvate

  • Compound

    amidotriphosphate

  • Compound

    diamidophosphate

  • Compound

    phosphoenol pyruvaldehyde

  • Compound

    phosphoenol pyruvaldehyde cyanohydrin

  • Compound

    phosphoenol dioxobutyramide

  • Compound

    glycolic acid phosphate

  • Compound

    glycolic acid

  • Compound

    phosphenol pyruvyl cyanide

  • Compound

    glycolaldehyde-2-phosphate cyanohydrin

  • Compound

    glyceramide 3-phosphate

  • Compound

    phosphoserine aminonitrile

  • Compound

    phosphoserine amide

  • Compound

    chloroacetic acid

  • Compound

    chloropyruvate

  • Compound

    acetic acid

  • Compound

    dihydroxyacetone phosphate

  • Compound

    Acetyl coenzyme A

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Acknowledgements

In memoriam of Harry Lonsdale. This work was supported by the Simons Foundation (31881), the Engineering and Physical Sciences Research Council (EPSRC (EP/K004980/1)), the Leverhulme Trust (RGP-2013-189) and an award from the Origin of Life Challenge.

Author information

Affiliations

  1. Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK

    • Adam J. Coggins
    •  & Matthew W. Powner

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Contributions

The research was conceived by M.W.P. Experiments were conducted by A.J.C. Both authors contributed to the design and analysis of experiments, and to writing the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Matthew W. Powner.

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