Prebiotic iron–sulfur peptide catalysts generate a pH gradient across model membranes of late protocells

Abstract

Prebiotic chemistry was likely mediated by metals, but how such prebiotic chemistry progressed into the metabolic-like networks needed to sustain life remains unclear. Here we experimentally delineate a potential path from prebiotically plausible iron–sulfur peptide catalysts to the types of pH gradients exploited by all known living organisms. Iron–sulfur peptides cooperatively accept electrons from NADH in a manner that is only partially mediated by ionic interactions. The electrons are then either passed to a terminal electron acceptor, such as hydrogen peroxide, or to an intermediate carrier, such as ubiquinone. The reduction of hydrogen peroxide leads to the production of hydroxide, which then contributes to the formation of a pH gradient across late protocell membranes. The data are consistent with the activity of prebiotic iron–sulfur peptide catalysts providing a selective advantage by equipping protocells with a pathway that connects catabolism to anabolism.

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Fig. 1: The effect of ligand occlusion and iron–sulfur nuclearity on the oxidation of NADH.
Fig. 2: Oxidation of NADH by Fe(iii) peptides.
Fig. 3: Proton gradient across vesicle membranes.
Fig. 4: Electron transfer at vesicle membranes.
Fig. 5: Schematic showing the path of electron transfer.

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Acknowledgements

Funding from the Simons Foundation (290358 to S.S.M), the Armenise–Harvard Foundation (to S.S.M.) and COST actions CM1304 (to C.B. and S.S.M.) and CA15133 (to S.S.M.) is gratefully acknowledged. We thank J. D. Sutherland, A. Mariani, G. Petris, M. Forlin, O. D. Toparlak, V. Vaida, S. Ranjan and Y. Bozzi for helpful discussions and L. Valer, C. Del Bianco (Protein Technology Facility) and G. Scarduelli (Advanced Imaging Facility) for help with preliminary experiments, protein purification and microscopy, respectively.

Authors contributions

C.B. and S.S.M. designed the experiments. Redox experiments, peptide synthesis and vesicle studies were performed by C.B. and E.G. Electrochemistry was performed and analysed by C.B., M.C. and F.F.D.B. HPLC assays were performed and analysed by C.B. and G.G. The manuscript was written by C.B. and S.S.M. and edited by all the authors.

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Correspondence to Sheref S. Mansy.

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Bonfio, C., Godino, E., Corsini, M. et al. Prebiotic iron–sulfur peptide catalysts generate a pH gradient across model membranes of late protocells. Nat Catal 1, 616–623 (2018). https://doi.org/10.1038/s41929-018-0116-3

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