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

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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.

References

  1. 1

    Eschenmoser, A. Etiology of potentially primordial biomolecular structures: from vitamin B12 to the nucleic acids and an inquiry into the chemistry of life's origin: a retrospective. Angew. Chem. Int. Ed. 50, 12412–12472 (2011).

    CAS  Article  Google Scholar 

  2. 2

    Sutherland, J. D. The origin of life—out of the blue. Angew. Chem. Int. Ed. 55, 104–121 (2016).

    CAS  Article  Google Scholar 

  3. 3

    Powner, M. W., Gerland, B. & Sutherland, J. D. Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 459, 239–242 (2009).

    CAS  Article  Google Scholar 

  4. 4

    Joyce, G. F. The antiquity of RNA-based evolution. Nature 418, 214–221 (2002).

    CAS  Article  Google Scholar 

  5. 5

    Benner, S. A., Kim, H.-Y. & Yang, Z. Setting the stage: the history, chemistry and geology behind RNA. Cold Spring Harb. Perspect. Biol. 4, a003541 (2012).

    Article  Google Scholar 

  6. 6

    Robertson, M. P. & Joyce, G. F. The origins of the RNA world. Cold Spring Harb. Perspect. Biol. 4, a003608 (2012).

    Article  Google Scholar 

  7. 7

    Krishnamurthy, R. On the emergence of RNA. Isr. J. Chem. 55, 837–850 (2015).

    CAS  Article  Google Scholar 

  8. 8

    Johnson, A. P. et al. The Miller volcanic spark discharge experiment. Science 322, 404 (2008).

    CAS  Article  Google Scholar 

  9. 9

    Chyba, C. & Sagan, C. Endogenous production, exogenous delivery and impact-shock synthesis of organic molecules: an inventory for the origins of life. Nature 355, 125–132 (1992).

    CAS  Article  Google Scholar 

  10. 10

    Miller, S. L. Production of amino acids under possible primitive Earth conditions. Science 117, 528–529 (1953).

    CAS  Article  Google Scholar 

  11. 11

    Pizzarello, S., Cooper, G. & Flynn, G. in Meteorites and the Early Solar System II (eds Lauretta, D. S. & McSween, H. Y. Jr) 625–651 (Univ. Arizona Press, 2006).

    Google Scholar 

  12. 12

    Wolman, Y., Haverland, W. J. & Miller, S. L. Nonprotein amino acids from spark discharges and their comparison with the Murchison meteorite amino acids. Proc. Natl Acad. Sci. USA 69, 809–811 (1972).

    CAS  Article  Google Scholar 

  13. 13

    Patel, B. H., Percivalle, C., Ritson, D. J., Duffy, C. D. & Sutherland, J. D. Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism. Nat. Chem. 7, 301–307 (2015).

    CAS  Article  Google Scholar 

  14. 14

    Powner, M. W., Zheng, S. L. & Szostak, J. W. Multicomponent assembly of proposed DNA precursors in water. J. Am. Chem. Soc. 134, 13889–13895 (2012).

    CAS  Article  Google Scholar 

  15. 15

    Shapiro, R. Prebiotic ribose synthesis: a critical analysis. Origin Life Evol. Biosphere 18, 71–85 (1988).

    CAS  Article  Google Scholar 

  16. 16

    Ricardo, A., Carrigan, M. A., Olcott, A. N. & Benner, S. A. Borate minerals stabilize ribose. Science 303, 196 (2004).

    CAS  Article  Google Scholar 

  17. 17

    Breslow, R. & Cheng, Z. L. L-Amino acids catalyze the formation of an excess of D-glyceraldehyde, and thus of other D-sugars, under credible prebiotic conditions. Proc. Natl Acad. Sci. USA 107, 5723–5725 (2010).

    CAS  Article  Google Scholar 

  18. 18

    Sagi, V. S. et al. Exploratory experiments on the chemistry of the ‘glyoxylate scenario’: formation of ketosugars from dihydroxyfumarate. J. Am. Chem. Soc. 134, 3577–3589 (2012).

    CAS  Article  Google Scholar 

  19. 19

    Islam, S. et al. Detection of potential TNA and RNA nucleoside precursors in a prebiotic mixture by pure shift diffusion-ordered NMR spectroscopy. Chem. Eur. J. 19, 4586–4595 (2013).

    CAS  Article  Google Scholar 

  20. 20

    Meinert, C. et al. Ribose and related sugars from ultraviolet irradiation of interstellar ice analogs. Science 352, 208–212 (2016).

    CAS  Article  Google Scholar 

  21. 21

    Becker, S. et al. A high-yielding, strictly regioselective prebiotic purine nucleoside formation pathway. Science 352, 833–836 (2016).

    CAS  Article  Google Scholar 

  22. 22

    Springsteen, G. & Joyce, G. F. Selective derivatization and sequestration of ribose from a prebiotic mix. J. Am. Chem. Soc. 126, 9578–9583 (2004).

    CAS  Article  Google Scholar 

  23. 23

    Anastasi, C., Crowe, M. A., Powner, M. W. & Sutherland, J. D. Direct assembly of nucleoside precursors from two- and three-carbon units. Angew. Chem. Int. Ed. 45, 6176–6179 (2006).

    CAS  Article  Google Scholar 

  24. 24

    Powner, M. W. & Sutherland, J. D. Phosphate-mediated interconversion of ribo- and arabino-configured prebiotic nucleotide intermediates. Angew. Chem. Int. Ed. 49, 4641–4643 (2010).

    CAS  Article  Google Scholar 

  25. 25

    Powner, M. W., Sutherland, J. D. & Szostak, J. W. Chemoselective multicomponent one-pot assembly of purine precursors in water. J. Am. Chem. Soc. 132, 16677–16688 (2010).

    CAS  Article  Google Scholar 

  26. 26

    Saul, R. et al. Reaction of 1,3-disubstituted acetone derivatives with pseudohalides: a simple approach to spiro[4.4]nonane-type bis-oxazolidines and -imidazolidines (bicyclic carbamates, thiocarbamates, ureas, and thioureas). Eur. J. Org. Chem. 1, 205–209 (2000).

    Article  Google Scholar 

  27. 27

    Nagorski, R. W. & Richard, J. P. Mechanistic imperatives for aldose-ketose isomerization in water: specific, general base- and metal-ion-catalyzed isomerization of glyceraldehyde with proton and hydride transfer. J. Am. Chem. Soc. 123, 794–802 (2001).

    CAS  Article  Google Scholar 

  28. 28

    Budin, I. & Szostak, J. W. Expanding roles for diverse physical phenomena during the origin of life. Annu. Rev. Biophys. 39, 245–263 (2010).

    CAS  Article  Google Scholar 

  29. 29

    Sagan, C. & Khare, B. N. Long-wavelength ultraviolet photoproduction of amino acids on the primitive Earth. Science 173, 417–420 (1971).

    CAS  Article  Google Scholar 

  30. 30

    Catsimpoolas, N. & Wood, J. L. Specific cleavage of cystine peptides by cyanide. J. Biol. Chem. 241, 1790–1796 (1966).

    CAS  PubMed  Google Scholar 

  31. 31

    Serianni, A. S., Nunez, H. A. & Barker, R. Cyanohydrin synthesis: studies with [13C]cyanide. J. Org. Chem. 45, 3329–3341 (1980).

    CAS  Article  Google Scholar 

  32. 32

    Schwartz, A. W. Intractable mixtures and the origin of life. Chem. Biodiv. 4, 656–664 (2007).

    CAS  Article  Google Scholar 

  33. 33

    Schwartz, A. W. Evaluating the plausibility of prebiotic multistage syntheses. Astrobiology 13, 784–789 (2013).

    Article  Google Scholar 

  34. 34

    Knight, R. D. & Landweber, L. F. The early evolution of the genetic code. Cell 101, 569–572 (2000).

    CAS  Article  Google Scholar 

  35. 35

    Hein, J. E., Tse, E. & Blackmond, D. G. A route to enantiopure RNA precursors from nearly racemic starting materials. Nat. Chem. 3, 704–706 (2011).

    CAS  Article  Google Scholar 

Download references

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.

Author information

Affiliations

Authors

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.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

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)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Islam, S., Bučar, D. & 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

Download citation

Further reading

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing