Mais uma hipótese sobre a origem da vida: síntese prebiótica divergente de pirimidina e ribonucleotídeos 8-oxo-purina

sábado, maio 20, 2017

Divergent prebiotic synthesis of pyrimidine and 8-oxo-purine ribonucleotides

Shaun Stairs, Arif Nikmal, Dejan-Krešimir Bučar, Shao-Liang Zheng, Jack W. Szostak & Matthew W. Powner

Nature Communications 8, Article number: 15270 (2017)

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Organic chemistryChemical origin of life

Received: 20 December 2016 Accepted: 15 March 2017

Published online: 19 May 2017

Figure 1: Proposed prebiotic ribonucleotide synthesis by divergent nucleobase assembly on a universal furanosyl-oxazoline scaffold.


Understanding prebiotic nucleotide synthesis is a long standing challenge thought to be essential to elucidating the origins of life on Earth. Recently, remarkable progress has been made, but to date all proposed syntheses account separately for the pyrimidine and purine ribonucleotides; no divergent synthesis from common precursors has been proposed. Moreover, the prebiotic syntheses of pyrimidine and purine nucleotides that have been demonstrated operate under mutually incompatible conditions. Here, we tackle this mutual incompatibility by recognizing that the 8-oxo-purines share an underlying generational parity with the pyrimidine nucleotides. We present a divergent synthesis of pyrimidine and 8-oxo-purine nucleotides starting from a common prebiotic precursor that yields the β-ribo-stereochemistry found in the sugar phosphate backbone of biological nucleic acids. The generational relationship between pyrimidine and 8-oxo-purine nucleotides suggests that 8-oxo-purine ribonucleotides may have played a key role in primordial nucleic acids prior to the emergence of the canonical nucleotides of biology.


This work was supported in part by the Simons Foundation (318881 to M.W.P. and 290363 to J.W.S.), the Engineering and Physical Sciences Research Council (EP/K004980/1 to M.W.P.) and through an award from the Origin of Life Challenge (to M.W.P.) and a UCL Excellence Fellowship (to D.-K.B.). We thank Dr K. Karu for assistance with Mass Spectrometry and Dr A.E. Aliev for assistance with NMR spectroscopy. J.W.S. is an Investigator of the Howard Hughes Medical Institute.

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Shaun Stairs & Arif Nikmal

These authors contributed equally to this work.


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

Shaun Stairs, Arif Nikmal, Dejan-Krešimir Bučar & Matthew W. Powner

Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA

Shao-Liang Zheng & Jack W. Szostak

Department of Molecular Biology and Center for Computational and Integrative Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA

Jack W. Szostak


M.W.P. conceived the research. M.W.P., J.W.S., S.S. and A.N. designed and analysed the experiments. M.W.P, S.S. and A.N. conducted the experiments. D.-K.B. and S.-L.Z. performed the crystallographic analyses. M.W.P, J.W.S. and S.S. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Matthew W. Powner.