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Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism

Nature Chemistry 7, 301–307 (2015) | Download Citation

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Abstract

A minimal cell can be thought of as comprising informational, compartment-forming and metabolic subsystems. To imagine the abiotic assembly of such an overall system, however, places great demands on hypothetical prebiotic chemistry. The perceived differences and incompatibilities between these subsystems have led to the widely held assumption that one or other subsystem must have preceded the others. Here we experimentally investigate the validity of this assumption by examining the assembly of various biomolecular building blocks from prebiotically plausible intermediates and one-carbon feedstock molecules. We show that precursors of ribonucleotides, amino acids and lipids can all be derived by the reductive homologation of hydrogen cyanide and some of its derivatives, and thus that all the cellular subsystems could have arisen simultaneously through common chemistry. The key reaction steps are driven by ultraviolet light, use hydrogen sulfide as the reductant and can be accelerated by Cu(I)–Cu(II) photoredox cycling.

  • Compound C2H4O2

    glycolaldehyde

  • Compound CH2N2

    cyanamide

  • Compound C3H4N2O

    2-aminooxazole

  • Compound C3H6O3

    glyceraldehyde

  • Compound C6H10N2O4

    D-arabinofuranosyl aminooxazoline

  • Compound C3HN

    cyanoacetylene

  • Compound C9H12N3O4+

    β-D-arabinofuranosyl-2,2'-anhydrocytidine

  • Compound CH4N2O

    urea

  • Compound C9H11N3O7P-

    α-D-ribofuranosyl cytidine-2',3'-cyclic phosphate

  • Compound C9H10N2O8P-

    α-D-ribofuranosyl uridine-2',3'-cyclic phosphate

  • Compound CHN

    hydrogen cyanide

  • Compound H2S

    hydrogen sulfide

  • Compound C2H4N2

    2-aminoacetonitrile

  • Compound C3H6N2O

    2-amino-3-hydroxypropanenitrile

  • Compound C3H6N2

    2-aminopropanenitrile

  • Compound C4H8N2O

    2-amino-3-hydroxybutanenitrile

  • Compound C3H6O3

    dihydroxyacetone

  • Compound C3H6O

    acetone

  • Compound C3H8O3

    glycerol

  • Compound C3H6O5P-

    glycerol-1,2-cyclic phosphate

  • Compound C3H7O6P2-

    glycerol-1-phosphate

  • Compound C3H7O6P2-

    glycerol-2-phosphate

  • Compound C4H7NO

    2-hydroxy-2-methylpropanenitrile

  • Compound C4H9NOS

    2-hydroxy-2-methylpropanethioamide

  • Compound C4H9NS

    2-methylpropanethioamide

  • Compound C5H9NO

    2-hydroxy-3-methylbutanenitrile

  • Compound C5H10N2

    2-amino-3-methylbutanenitrile

  • Compound C5H11NOS

    2-hydroxy-3-methylbutanethioamide

  • Compound C5H11NS

    3-methylbutanethioamide

  • Compound C6H11NO

    2-hydroxy-4-methylpentanenitrile

  • Compound C6H12N2

    2-amino-4-methylpentanenitrile

  • Compound C2H2

    acetylene

  • Compound C3H3N

    acrylonitrile

  • Compound C3H6N2

    3-aminopropanenitrile

  • Compound C4H9N4+

    amino((2-cyanoethyl)amino)methaniminium

  • Compound C3H7NO

    3-aminopropanal

  • Compound C4H10N3O+

    4-hydroxytetrahydropyrimidin-2(1H)-iminium

  • Compound C4H8N2O

    4-amino-2-hydroxybutanenitrile

  • Compound C5H11N4O+

    amino((3-cyano-3-hydroxypropyl)amino)methaniminium

  • Compound C5H13N4OS+

    amino((4-amino-3-hydroxy-4-thioxobutyl)amino)methaniminium

  • Compound C4H10N2OS

    4-amino-2-hydroxybutanethioamide

  • Compound C4H7NOS

    3-hydroxypyrrolidine-2-thione

  • Compound C5H13N4S+

    amino((4-amino-4-thioxobutyl)amino)methaniminium

  • Compound C4H7NS

    pyrrolidine-2-thione

  • Compound C6H13N4O+

    amino((4-cyano-4-hydroxybutyl)amino)methaniminium

  • Compound C6H14N5+

    amino((4-amino-4-cyanobutyl)amino)methaniminium

  • Compound C5H8N2

    pyrrolidine-2-carbonitrile

  • Compound C4H2N2

    maleonitrile

  • Compound C4H5N3

    2-aminosuccinonitrile

  • Compound C4H4N2O

    2-hydroxysuccinonitrile

  • Compound C4H4N2

    succinonitrile

  • Compound C4H5NO

    4-oxobutanenitrile

  • Compound C5H6N2O

    2-hydroxypentanedinitrile

  • Compound C5H7N3

    2-aminopentanedinitrile

  • Compound C3H5NO2

    2,3-dihydroxypropanenitrile

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Acknowledgements

In memoriam Harry Lonsdale. This work was supported by the Medical Research Council (No. MC_UP_A024_1009), a grant from the Simons Foundation (No. 290362 to J.D.S.) and an award from the Origin of Life Challenge.

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  1. MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK

    • Bhavesh H. Patel
    • , Claudia Percivalle
    • , Dougal J. Ritson
    • , Colm D. Duffy
    •  & John D. Sutherland

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Contributions

J.D.S. supervised the research and the other authors performed the experiments. All the authors contributed intellectually as the project unfolded. J.D.S. wrote the paper and B.H.P. and C.P. assembled the Supplementary Information, additionally incorporating data from D.J.R. and C.D.D.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to John D. Sutherland.

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DOI

https://doi.org/10.1038/nchem.2202