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)
Download Citation
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.
Abstract
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.
Acknowledgements
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.
Author information
Author notes
Shaun Stairs & Arif Nikmal
These authors contributed equally to this work.
Affiliations
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
Contributions
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 .
FREE PDF GRATIS: Nature Communications Sup. Info. Reviewers file
