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Metals promote sequences of the reverse Krebs cycle

Nature Ecology & Evolution volume 1, pages 1716–1721 (2017)Cite this article

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Abstract

The reverse tricarboxylic acid (rTCA) cycle (also known as the reverse Krebs cycle) is a central anabolic biochemical pathway whose origins are proposed to trace back to geochemistry, long before the advent of enzymes, RNA or cells, and whose imprint remains intimately embedded in the structure of core metabolism. If it existed, a primordial version of the rTCA cycle would necessarily have been catalysed by naturally occurring minerals at the earliest stage of the transition from geochemistry to biochemistry. Here, we report non-enzymatic promotion of multiple reactions of the rTCA cycle in consecutive sequence, whereby 6 of its 11 reactions were promoted by Zn2+, Cr3+ and Fe0 in an acidic aqueous solution. Two distinct three-reaction sequences were achieved under a common set of conditions. Selectivity was observed for reduction reactions producing rTCA cycle intermediates compared with those leading off-cycle. Reductive amination of ketoacids to furnish amino acids was observed under similar conditions. The emerging reaction network supports the feasibility of primitive anabolism in an acidic, metal-rich reducing environment.

The reductive coupling of two molecules of CO2 to acetate (1), equivalent to the AcCoA pathway, has been observed under aqueous conditions either by using Fe0 nanoparticles as reducing agents or through electrochemistry on greigite electrodes, albeit in small quantities and with poor selectivity27,28,29. Production of 1 from CO and MeSH in the presence of (Fe,Ni)S has also been reported30. Experimental efforts to test the plausibility of a prebiotic rTCA cycle have not been as encouraging31,32. Thus far, only two non-consecutive steps of the rTCA cycle (steps C and E in Fig. 1) have been reported with a greater than 5% yield under plausibly prebiotic conditions using mineral photocatalysis32. Notably, pyruvate (2) has been observed in low yields under electrochemical28 and CO-rich hydrothermal conditions33. Further efforts are needed to test the plausibility of an abiotic (complete or incomplete) rTCA cycle which, when viewed together with an abiotic AcCoA pathway, would provide a satisfying theory for the origin and organization of modern biochemistry. Here, we describe our efforts to assess the prebiotic viability of the six reduction and (de)hydration steps of the rTCA cycle under the influence of metals and metal ions34.

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Fig. 1: Hypothetical proto-anabolic network consisting of the AcCoA pathway (CO2 to AcCoA) and the rTCA cycle.
Fig. 2: Plausible chemical mechanisms.
Fig. 3: Prebiotic reaction network.

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Acknowledgements

This study received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement 639170). Further funding was provided by a grant from LabEx ‘Chemistry of Complex Systems’. We thank the ELSI Origins Network, which is supported by a grant from the John Templeton Foundation provided through the Earth-Life Science Institute of the Tokyo Institute of Technology. We thank E. Smith for stimulating discussions. This paper is dedicated to the memory of H. J. Morowitz.

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  1. Institute of Supramolecular Science and Engineering (ISIS UMR 7006), University of Strasbourg, National Center for Scientific Research (CNRS), F-67000, Strasbourg, France

    Kamila B. Muchowska, Sreejith J. Varma, Elodie Chevallot-Beroux, Lucas Lethuillier-Karl, Guang Li & Joseph Moran

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  1. Kamila B. Muchowska
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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. wrote the paper and K.B.M. assembled the Supplementary Information, incorporating data from S.J.V., E.C.-B. and L.L.-K. Important preliminary experiments were carried out by G.L.

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Correspondence to Joseph Moran.

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Supplementary Methods, Supplementary Figures 1–69, Supplementary Tables 1–7

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Muchowska, K.B., Varma, S.J., Chevallot-Beroux, E. et al. Metals promote sequences of the reverse Krebs cycle. Nat Ecol Evol 1, 1716–1721 (2017). https://doi.org/10.1038/s41559-017-0311-7

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