Metals promote sequences of the reverse Krebs cycle

  • Nature Ecology & Evolutionvolume 1pages17161721 (2017)
  • doi:10.1038/s41559-017-0311-7
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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.

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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.

Author information


  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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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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Joseph Moran.

Electronic supplementary material

  1. Supplementary Information

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