Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

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

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Reconstitution of the triose glycolysis pathway (blue nodes) in a mild prebiotically plausible aqueous reaction network controlled by α-phosphorylation.
Figure 2: Oxidation of phosphoenol pyruvaldehyde (9) and oxidative decarboxylation of pyruvates (6 and 19).
Figure 3: 1H NMR spectra (600 MHz, H2O/D2O 9:1, 25 °C) showing quantitative divergent synthesis of phosphoenol pyruvate (1)/glyceric acid 2-phosphate (4-2P) in 0.5 M phosphate buffer.
Figure 4: Divergent synthesis of glyceric acid 3-phosphate (4-3P) and phosphoserine (5-3P) from glycolaldehyde-2-phosphate (2-P).

Similar content being viewed by others

References

  1. Eschenmoser, A. & Loewenthal, E. Chemistry of potentially prebiological natural products. Chem. Soc. Rev. 21, 1–16 (1992).

    CAS  Google Scholar 

  2. Jeong, H., Tombor, B., Albert, R., Oltvai, Z. N. & Barabási, A. L. The large-scale organization of metabolic networks. Nature 407, 651–654 (2000).

    CAS  PubMed  Google Scholar 

  3. Oparin, A. I. The Origin of Life (MacMillan, 1938).

    Google Scholar 

  4. Huber, C. & Wächterhäuser, G. Activated acetic acid by carbon fixation on (Fe,Ni)S under primordial conditions. Science 276, 245–247 (1997).

    CAS  PubMed  Google Scholar 

  5. Miller, S. L., Schopf, J. W. & Lazcano, A. Oparin's ‘origin of life’: sixty years later. J. Mol. Evol. 44, 351–353 (1997).

    CAS  PubMed  Google Scholar 

  6. Morowitz, H. J., Kostelnik, J. D., Yang, J. & Cody, G. D. The origin of intermediary metabolism. Proc. Natl Acad. Sci. USA 97, 7704–7708 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhang, X. V. & Martin, S. T. Driving parts of Krebs cycle in reverse through mineral photochemistry. J. Am. Chem. Soc. 128, 16032–16033 (2006).

    CAS  PubMed  Google Scholar 

  8. Eschenmoser, A. On a hypothetical generational relationship between HCN and constituents of the reductive citric acid cycle. Chem. Biodiv. 4, 554–573 (2007).

    CAS  Google Scholar 

  9. Orgel, L. E. The implausibility of metabolic cycles on the prebiotic Earth. PLoS Biol. 6, 5–13 (2008).

    CAS  Google Scholar 

  10. Cooper, G., Reed, C., Nguyen, D., Carter, M. & Wang, Y. Detection and formation scenario of citric acid, pyruvic acid, and other possible metabolism precursors in carbonaceous meteorites. Proc. Natl Acad. Sci. USA 108, 14015–14020 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Sagi, V. N., Punna, V., Hu, F., Meher, G. & Krishnamurthy, R. Exploratory experiments on the chemistry of the ‘glyoxylate scenario’: formation of ketosugars from dihydroxyfumarate. J. Am. Chem. Soc. 134, 3577–3589 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Patel, B. H., Percivalle, C., Ritson, D. J., Duffy, C. D. & Sutherland, J. D. Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism. Nat. Chem. 7, 301–307 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. De Duve, C. Singularites: Landmarks on the Pathway of Life (Cambridge Univ. Press, 2005).

    Google Scholar 

  14. Powner, M. W. & Sutherland, J. D. Prebiotic chemistry: a new modus operandi. Phil. Trans. R. Soc. B 366, 2870–2877 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Nelson, D. L. & Cox, M. M. in Lehninger Principles of Biochemistry 4th edn, Ch. 13, 493–497 (W. H. Freeman 2004).

    Google Scholar 

  16. Walsh, C. T., Benson, T. E., Kim, D. H. & Lees, W. J. The versatility of phosphoenolpyruvate and its vinyl ether products in biosynthesis. Chem. Biol. 3, 83–91 (1996).

    CAS  PubMed  Google Scholar 

  17. Potter, S. & Fothergill-Gilmore, L. A. Molecular evolution: the origin of glycolysis. Biochem. Mol. Biol. Educ. 21, 45–48 (1993).

    CAS  Google Scholar 

  18. Powner, M. W., Gerland, B. & Sutherland, J. D. Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 459, 239–242 (2009).

    CAS  PubMed  Google Scholar 

  19. Cody, G. D. et al. Primordial carbonylated iron–sulfur compounds and the synthesis of pyruvate. Science 289, 1337–1340 (2000).

    CAS  PubMed  Google Scholar 

  20. Weber, A. The sugar model: catalysis by amines and amino acid products. Orig. Life Evol. Biosph. 31, 71–86 (2001).

    CAS  PubMed  Google Scholar 

  21. Keller, M. A., Turchyn, A. V. & Ralser, M. Non-enzymatic glycolysis and pentose phosphate pathway-like reactions in a plausible Archean ocean. Mol. Syst. Biol. 10, 725–737 (2014).

    PubMed  PubMed Central  Google Scholar 

  22. Guzman, M. I. & Martin, S. T. Prebiotic metabolism: production by mineral photoelectrochemistry of α-ketocarboxylic acids in the reductive tricarboxylic acid cycle. Astrobiology 9, 833–842 (2009).

    CAS  PubMed  Google Scholar 

  23. Kolb, V. & Orgel, L. E. Phosphorylation of glyceric acid in aqueous solution using trimetaphosphate. Orig. Life Evol. Biosph. 26, 7–13 (1996).

    CAS  PubMed  Google Scholar 

  24. Pasek, M. A., Kee, T. P., Bryant, D. E., Pavlov, A. A. & Lunine, J. I. Production of potentially prebiotic condensed phosphates by phosphorus redox chemistry. Angew. Chem. Int. Ed. 47, 7918–7920 (2008).

    CAS  Google Scholar 

  25. Krishnamurthy, R., Arrhenius, G. & Eschenmoser, A. Formation of glycolaldehyde phosphate from glycolaldehyde in aqueous solution. Orig. Life Evol. Biosph. 29, 333–354 (1999).

    CAS  PubMed  Google Scholar 

  26. Rabinowitz, J., Lores, J., Krebsbach, R. & Rogers, G. Peptide formation in the presence of linear or cyclic polyphosphates. Nature 224, 795–796 (1969).

    CAS  PubMed  Google Scholar 

  27. Saffhill, R. Selective phosphorylation of the cis-2′,3′-diol of unprotected ribonucleosides with trimetaphosphate in aqueous solution. J. Org. Chem. 36, 2881–2883 (1970).

    Google Scholar 

  28. Mullen, L. B. & Sutherland, J. D. Formation of potentially prebiotic amphiphiles by reaction of β-hydroxy-n-alkylamines with cyclotriphosphate. Angew. Chem. Int. Ed. 46, 4166–4168 (2007).

    CAS  Google Scholar 

  29. Orgel, L. E. Prebiotic chemistry and the origin of the RNA world. Crit. Rev. Biochem. Mol. Biol. 39, 99–123 (2004).

    CAS  PubMed  Google Scholar 

  30. Keefe, A. D. & Miller, S. L. Are polyphosphates or phosphate esters prebiotic reagents? J. Mol. Evol. 41, 693–702 (1995).

    CAS  PubMed  Google Scholar 

  31. Sutherland, J. D., Mullen, L. B. & Buchet, F. F. Potentially prebiotic Passerini-type reactions of phosphates. Synlett 14, 2161–2163 (2008).

    Google Scholar 

  32. Krishnamurthy, R., Guntha, S. & Eschenmoser, A. Regioselective α-phosphorylation of aldoses in aqueous solution. Angew. Chem. Int. Ed. 39, 2281–2285 (2000).

    CAS  Google Scholar 

  33. Muller, D. et al. Chemie von α-Aminonitrilen. Aldomerisierung von Glycolaldehyd-phosphat zu racemischen Hexose-2,4,6-triphosphaten und (in Gegenwart von Formaldehyd) racemischen Pentose-2,4-diphosphaten: rac-Allose-2,4,6-triphosphat und rac-Ribose-2,4-diphosphat sind die Reaktionshauptprodukte. Helv. Chim. Acta 73, 1410–1468 (1990).

    Google Scholar 

  34. Eschenmoser, A. Chemical etiology of nucleic acid structure. Science 284, 2118–2124 (1999).

    CAS  PubMed  Google Scholar 

  35. Corey, E. J., Gilman, N. W. & Ganem, B. E. New methods for the oxidation of aldehydes to carboxylic acids and esters. J. Am. Chem. Soc. 90, 5616–5617 (1968).

    CAS  Google Scholar 

  36. Goldman, N., Reed, E. J., Fried, L. E., William Kuo, I.-F. & Maiti, A. Synthesis of glycine-containing complexes in impacts of comets on early Earth. Nat. Chem. 2, 949–954 (2010).

    CAS  PubMed  Google Scholar 

  37. Öberg, K. I. et al. The comet-like composition of a protoplanetary disk as revealed by complex cyanides. Nature 520, 198–201 (2015).

    PubMed  Google Scholar 

  38. Osterberg, R. Origins of metal ions in biology. Nature 249, 382–383 (1974).

    CAS  PubMed  Google Scholar 

  39. Braterman, P. S., Cairns-Smith, A. G. & Sloper, R. W. Photo-oxidation of hydrated Fe2+-significance for banded iron formations. Nature 303, 163–164 (1983).

    CAS  Google Scholar 

  40. Liu, R. & Orgel, L. E. Oxidative acylation using thioacids. Nature 389, 52–54 (1997).

    CAS  PubMed  Google Scholar 

  41. Keefe, A. D. & Miller, S. L. Was ferrocyanide a prebiotic reagent? Orig. Life Evol. Biosph. 26, 111–129 (1996).

    CAS  PubMed  Google Scholar 

  42. Bowler, F. R. et al. Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation. Nat. Chem. 5, 383–389 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Rudnick, R. L. & Fountain, D. M. Nature and composition of the continental crust: a lower crustal perspective. Rev. Geophys. 33, 267–309 (1995).

    Google Scholar 

  44. Post, J. E. Manganese oxide minerals: crystal structures and economic and environmental significance. Proc. Natl Acad. Sci. USA 96, 3447–3454 (1997).

    Google Scholar 

  45. Tebo, B. M. et al. Biogenic manganese oxides: properties and mechanisms of formation. Annu. Rev. Earth Planet. Sci. 32, 287–328 (2004).

    CAS  Google Scholar 

  46. Hazen, R. M. et al. Mineral evolution. Am. Mineral. 93, 1693–1720 (2008).

    CAS  Google Scholar 

  47. Maynard, J. B. The chemistry of manganese ores through time: a signal of increasing diversity of Earth-surface environments. Econ. Geol. 105, 535–552 (2010).

    CAS  Google Scholar 

  48. Trail, D., Watson, E. B. & Tailby, N. D. The oxidation state of Hadean magmas and implications for early Earth's atmosphere. Nature 480, 79–82 (2011).

    CAS  PubMed  Google Scholar 

  49. Hazen, R. Paleomineralogy of the Hadean eon: a preliminary species list. Am. J. Sci. 13, 807–843 (2013).

    Google Scholar 

  50. Anbar, A. D. & Holland, H. D. The photochemistry of manganese and the origin of banded iron formations. Geochim. Cosmochim. Acta 56, 2595–2603 (1992).

    CAS  PubMed  Google Scholar 

  51. Chatgilialoglu, C., Crich, D., Komatsu, M. & Ryu, I. Chemistry of acyl radicals. Chem. Rev. 99, 1991–2069 (1999).

    CAS  PubMed  Google Scholar 

  52. Kasting, J. F., Holland, H. D. & Pinto, J. R. Oxidant abundances in rainwater and the evolution of atmospheric oxygen. J. Geophys. Res. 90, 10497–10510 (1987).

    Google Scholar 

  53. Forsythe, J. G. et al. Ester-mediated amide bond formation driven by wet–dry cycles: a possible path to polypeptides on the prebiotic Earth. Angew Chem. Int. Ed. 54, 9871–9875 (2015).

    CAS  Google Scholar 

  54. Kim, Y. S., Wo, K. P., Maity, S., Atreya, S. K. & Kaiser, R. I. Radiation-induced formation of chlorine oxides and their potential role in the origin of Martian perchlorates. J. Am. Chem. Soc. 135, 4910–4913 (2013).

    CAS  PubMed  Google Scholar 

  55. Leshin, L. A. et al. Volatile, isotope, and organic analysis of Martian fines with the Mars Curiosity rover. Science 341, 6153–6162 (2013).

    Google Scholar 

  56. Solomon, S., Sanders, R. W., Garcia, R. R. & Keys, J. G. Increased chlorine dioxide over Antarctica caused by volcanic aerosols from Mount Pinatubo. Nature 363, 245–248 (1993).

    CAS  Google Scholar 

  57. Jackson, W. A. et al. Widespread occurrence of (per)chlorate in the Solar System. Earth Planet Sci. Lett. 430, 470–476 (2015).

    CAS  Google Scholar 

  58. Halperin, J. & Taube, H. The transfer of oxygen atoms in oxidation–reduction reactions. III. The reaction of halogenates with sulfite in aqueous solution. J. Am. Chem. Soc. 74, 375–380 (1952).

    CAS  Google Scholar 

  59. Bal, B. S., Childers, W. E. & Pinnick, H. W. Oxidation of α,β-unsaturated aldehydes. Tetrahedron 37, 2091–2096 (1981).

    CAS  Google Scholar 

  60. Pascal, R., Taillades, J. & Commeyras, A. Strecker's and related systems. IX. Acetone as catalyst for the hydration of tertiary α-aminonitriles in aqueous basic solution. Bull. Soc. Chim. Fr. 2, 177–184 (1978).

    Google Scholar 

  61. Nwaukwa, S. O. & Keehn, P. M. Oxidative cleavage of α-diols, α-diones, α-hydroxyketones and α-hydroxy- and α-ketone-acids with calcium hypochlorite. Tetrahedron Lett. 23, 3135–3138 (1982).

    CAS  Google Scholar 

  62. Keefe, A. D., Newton, G. L. & Miller, S. L. A possible prebiotic synthesis of pantetheine, a precursor to coenzyme A. Nature 373, 683–685 (1995).

    CAS  PubMed  Google Scholar 

  63. Nargoski, R. W. & Richard, J. P. Mechanistic imperatives for aldose–ketose isomerization in water: specific, general base- and metal ion-catalyzed isomerization of glyceraldehyde with proton and hydride transfer. J. Am. Chem. Soc. 123, 794–802 (2001).

    Google Scholar 

Download references

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

Authors and Affiliations

Authors

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.

Corresponding author

Correspondence to Matthew W. Powner.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 7774 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Coggins, A., Powner, M. Prebiotic synthesis of phosphoenol pyruvate by α-phosphorylation-controlled triose glycolysis. Nature Chem 9, 310–317 (2017). https://doi.org/10.1038/nchem.2624

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.2624

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing