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Prebiotic selection and assembly of proteinogenic amino acids and natural nucleotides from complex mixtures

Nature Chemistry volume 9, pages 584–589 (2017)Cite this article

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Abstract

A central problem for the prebiotic synthesis of biological amino acids and nucleotides is to avoid the concomitant synthesis of undesired or irrelevant by-products. Additionally, multistep pathways require mechanisms that enable the sequential addition of reactants and purification of intermediates that are consistent with reasonable geochemical scenarios. Here, we show that 2-aminothiazole reacts selectively with two- and three-carbon sugars (glycolaldehyde and glyceraldehyde, respectively), which results in their accumulation and purification as stable crystalline aminals. This permits ribonucleotide synthesis, even from complex sugar mixtures. Remarkably, aminal formation also overcomes the thermodynamically favoured isomerization of glyceraldehyde into dihydroxyacetone because only the aminal of glyceraldehyde separates from the equilibrating mixture. Finally, we show that aminal formation provides a novel pathway to amino acids that avoids the synthesis of the non-proteinogenic α,α-disubstituted analogues. The common physicochemical mechanism that controls the proteinogenic amino acid and ribonucleotide assembly from prebiotic mixtures suggests that these essential classes of metabolite had a unified chemical origin.

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Figure 1: Prebiotic ribonucleotide synthesis.
Figure 2: Multiple pathways to 2-aminothiazole (7) in aqueous cyanosulfidic solution.
Figure 3: Selective C2-aminal 8 sequestration from a mixture of C2 and C3 sugars.
Figure 4: Convergent crystallization-controlled synthesis of pure ribo-1 from a complex mixture of sugars.
Figure 5: High-yielding 2-aminothiazole (7)-controlled selective aldehyde reactivity.

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Acknowledgements

This work was supported by the Simons Foundation (318881), the Engineering and Physical Sciences Research Council (EP/K004980/1), the Leverhulme Trust (RGP-2013-189) and through an award from the Origin of Life Challenge (M.W.P.) and a UCL Excellence Fellowship (D.-K.B.). The authors thank K. Karu for assistance with mass spectrometry and A. E. Aliev for assistance with NMR spectroscopy.

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Authors and Affiliations

  1. Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK

    Saidul Islam, Dejan-Krešimir Bučar & Matthew W. Powner

Authors
  1. Saidul Islam
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  2. Dejan-Krešimir Bučar
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  3. Matthew W. Powner
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Contributions

M.W.P. conceived the research. M.W.P. and S.I. designed and analysed the experiments. S.I. conducted the experiments. D.-K.B. performed the crystallographic analyses. M.W.P. and S.I. wrote the paper.

Corresponding author

Correspondence to Matthew W. Powner.

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Supplementary information

Supplementary information

Supplementary information (PDF 14342 kb)

Supplementary information

Crystallographic data for compound 8a. (CIF 15 kb)

Supplementary information

Structure factors file for compound 8a. (FCF 102 kb)

Supplementary information

Crystallographic data for compound rac-8b. (CIF 15 kb)

Supplementary information

Structure factors file for compound rac-8b. (FCF 70 kb)

Supplementary information

Crystallographic data for compound D-8b. (CIF 16 kb)

Supplementary information

Structure factors file for compound D-8b. (FCF 117 kb)

Supplementary information

Crystallographic data for compound L-8b. (CIF 16 kb)

Supplementary information

Structure factors file for compound L-8b. (FCF 103 kb)

Supplementary information

Crystallographic data for compound 8c. (CIF 17 kb)

Supplementary information

Structure factors file for compound 8c. (FCF 147 kb)

Supplementary information

Crystallographic data for compound 8d. (CIF 14 kb)

Supplementary information

Structure factors file for compound 8d. (FCF 105 kb)

Supplementary information

Crystallographic data for compound 8e. (CIF 13 kb)

Supplementary information

Structure factors file for compound 8e. (FCF 51 kb)

Supplementary information

Crystallographic data for compound 8f. (CIF 15 kb)

Supplementary information

Structure factors file for compound 8f. (FCF 128 kb)

Supplementary information

Crystallographic data for compound 8g. (CIF 19 kb)

Supplementary information

Structure factors file for compound 8g. (FCF 119 kb)

Supplementary information

Crystallographic data for compound 8m. (CIF 15 kb)

Supplementary information

Structure factors file for compound 8m. (FCF 149 kb)

Supplementary information

Crystallographic data for compound D-ribo-1. (CIF 15 kb)

Supplementary information

Structure factors file for compound D-ribo-1. (FCF 71 kb)

Supplementary information

Crystallographic data for compound L-ribo-1. (CIF 15 kb)

Supplementary information

Structure factors file for compound L-ribo-1. (FCF 71 kb)

Supplementary information

Crystallographic data for compound rac-ribo-1. (CIF 14 kb)

Supplementary information

Structure factors file for compound rac-ribo-1. (FCF 71 kb)

Supplementary information

Crystallographic data for compound rac-threo-5. (CIF 26 kb)

Supplementary information

Structure factors file for compound rac-threo-5. (FCF 299 kb)

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Islam, S., Bučar, DK. & Powner, M. Prebiotic selection and assembly of proteinogenic amino acids and natural nucleotides from complex mixtures. Nature Chem 9, 584–589 (2017). https://doi.org/10.1038/nchem.2703

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