Grefenstette, NM; (2017) Studies towards the prebiotic synthesis and phosphorylation of ribonucleotides. Doctoral thesis , UCL (University College London).

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Abstract

The discovery of the universality of life’s biochemistry across all domains of life suggests that life has a unified chemical origin. RNA is a highly versatile pillar of extant biochemistry, with essential and universal roles as a genetic messenger between DNA and proteins, a universally essential catalyst in ribosomes, and an essential element of a variety of co-factors. The deep-seated role of RNA in modern biochemistry and RNA's unique dual biological functionality, acting both genotypically and phenotypically, makes RNA a strong contender for the first biopolymer of life: the ‘RNA world’ hypothesis. However, one of the most significant problems in bridging the gap between a purely abiological and a biologically active world is a prebiotically plausible synthesis of ribonucleotides. An account of our results investigating novel prebiotically plausible syntheses of ribonucleotides is presented. We propose a new oxidative approach to the synthesis of nucleotide precursors exploiting the oxidation of acrolein, the simplest unsaturated aldehyde with many prebiotically plausible syntheses, to glycidaldehyde by aqueous hydrogen peroxide, a simple and prebiotically robust oxidant. Glycidaldehyde provides the activation required to realise regioselective incorporation of phosphate during nucleotide assembly, leading to the first prebiotically plausible aqueous synthesis of pyrimidine nucleotides 5′-phosphate. These reactions are effected under simple, mild, aqueous conditions, compatible with the rest of our prebiotic studies on the synthesis of amino acids and purine ribonucleotides. We also demonstrate that acrolein can be used in the prebiotic synthesis of C3 amino acids, establishing acrolein as a central synthon in prebiotic chemistry. Our discovery of a generational node in the network of prebiotic chemistry that links the syntheses of amino acids with nucleotides 5'-phosphates suggests that these different groups of metabolites need not have arisen from separate chemistries, helping us to get a better understanding of the processes governing the chemical evolution of life.

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