Conversion of biosynthetic precursors of RNA to those of DNA by photoredox chemistry

Abstract

Soon after the origin of RNA-based life, depletion of prebiotically synthesised ribonucleotides would have driven the evolution of a biosynthetic pathway to these key building blocks. Ribozyme-catalysed nucleosidation-the key biosynthetic step-requires that ribose and the nucleobases are produced by abiotic chemistry and are relatively stable to the conditions of their synthesis. The most plausible prebiotic synthesis of sugars involves photoreduction of cyanohydrins by hydrogen sulphide in the presence of copper(I) cyanide, and we therefore subjected ribose to these conditions whereupon it was partially converted to 2-deoxyribose. Furthermore, a derivative of uracil is reduced under similar conditions to thymine. Thus, DNA biosynthetic precursors can be formed abiotically from those of RNA allowing for an early evolutionary transition to life based on RNA and DNA.

Scheme 1

Systems chemistry synthesis of activated pyrimidine ribonucleotides

Fig. 1

Partial ¹H NMR analysis of the effect of exposing ribose (ribo-11) to the photoreduction conditions that generate the C₂ and C₃ sugars 6 and 8 from their cyanohydrin precursors 5 and 7. a Spectrum of ribose in D₂O. b Spectrum of the photoreduction products of ribose in H₂O-D₂O (with HOD signal suppression). c Spectrum of 2-deoxyribose 19 in D₂O. Full ¹H NMR spectra are shown in Supplementary Figs. S1a, b. The various tautomers of ribo-11 and 19 are indicated in parentheses: α and β refer to anomeric hydroxyl group stereochemistry; f and p refer to furanose and pyranose forms

Scheme 2

Prebiotic syntheses of 2-deoxyribose 19

Scheme 3

Chemistry of uracil 16 under the conditions of sugar synthesis