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Synthesis and breakdown of universal metabolic precursors promoted by iron

Nature volume 569, pages 104–107 (2019)Cite this article

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An Author Correction to this article was published on 17 April 2021

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Abstract

Life builds its molecules from carbon dioxide (CO2) and breaks them back down again through the intermediacy of just five metabolites, which are the universal hubs of biochemistry1. However, it is unclear how core biological metabolism began and why it uses the intermediates, reactions and pathways that it does. Here we describe a purely chemical reaction network promoted by ferrous iron, in which aqueous pyruvate and glyoxylate—two products of abiotic CO2 reduction2,3,4—build up 9 of the 11 intermediates of the biological Krebs (or tricarboxylic acid) cycle, including all 5 universal metabolic precursors. The intermediates simultaneously break down to CO2 in a life-like regime that resembles biological anabolism and catabolism5. Adding hydroxylamine6,7,8 and metallic iron into the system produces four biological amino acids in a manner that parallels biosynthesis. The observed network overlaps substantially with the Krebs and glyoxylate cycles9,10, and may represent a prebiotic precursor to these core metabolic pathways.

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Fig. 1: Fe2+-promoted synthesis and breakdown of the precursors of biological metabolism.
Fig. 2: Comparison of the observed reaction network with the TCA and glyoxylate cycles.

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Data availability

All data are available in the main text, Extended Data Figs. 1, 2 and the Supplementary Information (Supplementary Materials and Methods, Supplementary Figs. 1–29 and Supplementary Tables 1–4).

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References

  1. Braakman, R. & Smith, E. The compositional and evolutionary logic of metabolism. Phys. Biol. 10, 011001 (2013).

    Article  ADS  CAS  Google Scholar 

  2. Varma, S. J., Muchowska, K. B., Chatelain, P. & Moran, J. Native iron reduces CO2 to intermediates and end-products of the acetyl-CoA pathway. Nat. Ecol. Evol. 2, 1019–1024 (2018).

    Article  Google Scholar 

  3. Eggins, B. R., Brown, E. M., McNeill, E. A. & Grimshaw, J. Carbon dioxide fixation by electrochemical reduction in water to oxalate and glyoxylate. Tetrahedr. Lett. 29, 945–948 (1988).

    Article  CAS  Google Scholar 

  4. Marín-Yaseli, M. R., González-Toril, E., Mompeán, C. & Ruiz-Bermejo, M. The role of aqueous aerosols in the “glyoxylate scenario”: an experimental approach. Chemistry 22, 12785–12799 (2016).

    Article  Google Scholar 

  5. Goldford, J. E. & Segrè, D. Modern views of ancient metabolic networks. Curr. Opin. Syst. Biol. 8, 117–124 (2018).

    Article  Google Scholar 

  6. Canfield, D. E., Glazer, A. N. & Falkowski, P. G. The evolution and future of Earth’s nitrogen cycle. Science 330, 192–196 (2010).

    Article  ADS  CAS  Google Scholar 

  7. Kalson, N.-H., Furman, D. & Zeiri, Y. Cavitation-induced synthesis of biogenic molecules on primordial Earth. ACS Cent. Sci. 3, 1041–1049 (2017).

    Article  CAS  Google Scholar 

  8. Sakurai, M. & Yanagawa, H. Prebiotic synthesis of amino acids from formaldehyde and hydroxylamine in a modified sea medium. Orig. Life 14, 171–176 (1984).

    Article  ADS  CAS  Google Scholar 

  9. Muchowska, K. B. et al. Metals promote sequences of the reverse Krebs cycle. Nat. Ecol. Evol. 1, 1716–1721 (2017).

    Article  Google Scholar 

  10. Zubay, G. The glyoxylate cycle, a possible evolutionary precursor of the TCA cycle. Chemtracts 16, 783–788 (2003).

    CAS  Google Scholar 

  11. Ruiz-Mirazo, K., Briones, C. & de la Escosura, A. Prebiotic systems chemistry: new perspectives for the origins of life. Chem. Rev. 114, 285–366 (2014).

    Article  CAS  Google Scholar 

  12. Sutherland, J. D. Studies on the origin of life—the end of the beginning. Nat. Rev. Chem. 1, 0012 (2017).

    Article  CAS  Google Scholar 

  13. Harrison, S. & Lane, N. Life as a guide to prebiotic nucleotide synthesis. Nat. Commun. 9, 5176 (2018).

    Article  ADS  CAS  Google Scholar 

  14. Wächtershäuser, G. Evolution of the first metabolic cycles. Proc. Natl Acad. Sci. USA 87, 200–204 (1990).

    Article  ADS  Google Scholar 

  15. Smith, E. & Morowitz, H. J. Universality in intermediary metabolism. Proc. Natl Acad. Sci. USA 101, 13168–13173 (2004).

    Article  ADS  CAS  Google Scholar 

  16. Martin, W. F. & Russell, M. J. On the origin of biochemistry at an alkaline hydrothermal vent. Phil. Trans. R. Soc. Lond. B 362, 1887–1925 (2007).

    Article  CAS  Google Scholar 

  17. Hartman, H. Speculations on the origin and evolution of metabolism. J. Mol. Evol. 4, 359–370 (1975).

    Article  ADS  CAS  Google Scholar 

  18. Camprubi, E., Jordan, S., Vasiliadou, R. & Lane, N. Iron catalysis at the origin of life. IUBMB Life 69, 373–381 (2017).

    Article  CAS  Google Scholar 

  19. Roldan, A. et al. Bio-inspired CO2 conversion by iron sulfide catalysts under sustainable conditions. Chem. Commun. 51, 7501–7504 (2015).

    Article  CAS  Google Scholar 

  20. Keller, M. A., Kampjut, D., Harrison, S. A. & Ralser, M. Sulfate radicals enable a non-enzymatic Krebs cycle precursor. Nat. Ecol. Evol. 1, 0083 (2017).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Novikov, Y. & Copley, S. D. Reactivity landscape of pyruvate under simulated hydrothermal vent conditions. Proc. Natl Acad. Sci. USA 110, 13283–13288 (2013).

    Article  ADS  CAS  Google Scholar 

  23. Goldford, J. E., Hartman, H., Smith, T. F. & Segrè, D. Remnants of an ancient metabolism without phosphate. Cell 168, 1126–1134 (2017).

    Article  CAS  Google Scholar 

  24. Coggins, A. & Powner, M. Prebiotic synthesis of phosphoenol pyruvate by α-phosphorylation-controlled triose glycolysis. Nat. Chem. 9, 310–317 (2017).

    Article  CAS  Google Scholar 

  25. Springsteen, G., Yerabolu, J., Nelson, J., Rhea, C. & Krishnamurthy, R. Linked cycles of oxidative decarboxylation of glyoxylate as protometabolic analogs of the citric acid cycle. Nat. Commun. 9, 91 (2018).

    Article  ADS  Google Scholar 

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

    Article  Google Scholar 

  27. Rouxel, O. J., Bekker, A. & Edwards, K. J. Iron isotope constraints on the Archean and Paleoproterozoic ocean redox state. Science 307, 1088–1091 (2005).

    Article  ADS  CAS  Google Scholar 

  28. Eschenmoser, A. The search for the chemistry of life’s origin. Tetrahedron 63, 12821–12844 (2007).

    Article  CAS  Google Scholar 

  29. Mall, A. et al. Reversibility of citrate synthase allows autotrophic growth of a thermophilic bacterium. Science 359, 563–567 (2018).

    Article  ADS  CAS  Google Scholar 

  30. Nunoura, T. et al. A primordial and reversible TCA cycle in a facultatively chemolithoautotrophic thermophile. Science 359, 559–563 (2018).

    Article  ADS  CAS  Google Scholar 

  31. Orgel, L. E. The implausibility of metabolic cycles on the prebiotic Earth. PLoS Biol. 6, e18 (2008).

    Article  Google Scholar 

  32. Vasas, V., Szathmáry, E. & Santos, M. Lack of evolvability in self-sustaining autocatalytic networks constraints metabolism-first scenarios for the origin of life. Proc. Natl Acad. Sci. USA 107, 1470–1475 (2010).

    Article  ADS  CAS  Google Scholar 

  33. De Duve, C. Blueprint For a Cell: The Nature and Origin of Life (Neil Patterson Publishers, 1991).

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Acknowledgements

We thank W. F. Martin and D. Segrè for discussions. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement 639170) and from the French Agence Nationale de la Recherche (ANR) Laboratoires d’Excellence ‘Chemistry of Complex Systems’ (ANR-10-LABX-0026 CSC).

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Nature thanks Eric Smith, Peter Strazewski and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Université de Strasbourg, CNRS, ISIS, Strasbourg, France

    Kamila B. Muchowska, Sreejith J. Varma & Joseph Moran

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  1. Kamila B. Muchowska
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  2. Sreejith J. Varma
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  3. Joseph Moran
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Contributions

J.M. supervised the research and the other authors performed the experiments. All authors contributed intellectually throughout the study. J.M. and K.B.M wrote the paper, and K.B.M. and S.J.V. assembled the Supplementary Information.

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Correspondence to Joseph Moran.

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The authors declare no competing interests.

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Extended data figures and tables

Extended Data Fig. 1 Screen for transition metal promoters.

These GC chromatograms show the reaction networks that arise from pyruvate and glyoxylate at 70 °C, as promoted by different transition metal ions (qualitative screen).

Extended Data Fig. 2 Calibration lines for carboxylic acids.

Shown are the correlations between the concentrations of aqueous solutions of carboxylic acids (glyoxylic, glycolic, oxalic, malonic, levulinic, mesaconic, and hydroxyketoglutaric plus oxopentenedioic acids) and the measured GC peak area. Error bars correspond to the standard deviation (three independent runs). Orange lines show the 95% confidence bounds computed for second-degree polynomial fits (OriginPro). Calibration lines for glycine, aspartic acid and glutamic acid are shown in Supplementary Fig. 10. Calibration lines for the remaining compounds detected here (pyruvate, malate, fumarate, succinate, α-ketoglutarate, isocitrate, cis-aconitate, tricarballylate and alanine) are identical to those we reported previously for the same analytical set-up9 (Supplementary Table 1).

Supplementary information

Supplementary Information

This file contains Supplementary Materials and Methods, Supplementary References, Supplementary Figures 1-31 and Supplementary Tables 1-5.

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Muchowska, K.B., Varma, S.J. & Moran, J. Synthesis and breakdown of universal metabolic precursors promoted by iron. Nature 569, 104–107 (2019). https://doi.org/10.1038/s41586-019-1151-1

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