A minimal cell can be thought of as comprising informational, compartment-forming and metabolic subsystems. Imagining the abiotic assembly of such an overall system, however, places great demands on hypothetical prebiotic chemistry. The perceived differences and incompatibilities between these subsystems have led to the widely held assumption that one or other subsystem must have preceded the others. Here, we have experimentally investigated the validity of this assumption by examining the assembly of various biomolecular building blocks from prebiotically plausible intermediates and one-carbon feedstock molecules. We show that precursors of ribonucleotides, amino acids and lipids can all be derived by reductive homologation of hydrogen cyanide and some of its derivatives and thus that all the cellular subsystems could have arisen simultaneously through common chemistry. The key reaction steps are driven by UV light, use hydrogen sulfide as reductant and can be accelerated by Cu(I)-Cu(II) photoredox cycling.Viewing the cell as an ensemble of subsystems 1 begs the question 'did the subsystems emerge together, or one after the other at the origin of life?' The consensus that sequential emergence is more likely 2 (though with opinions differing as to which subsystem came first [3][4][5] ) has been based on the notion that different, mutually incompatible chemistries are needed to make the various subsystems. We set out to explore this experimentally by evaluating the assembly chemistry of the various subsystems. Investigation of the assembly chemistry of an informational subsystem based on RNA led to our discovery of an efficient synthesis of activated pyrimidine ribonucleotides 6 . In this synthesis (Fig. 1a, bold, blue arrows), the C 2 sugar glycolaldehyde 1 undergoes phosphate-catalysed condensation with cyanamide 2 to give 2-aminooxazole 3. This heterocycle then participates in a C-C bond Reprints and permissions information is available online at www.nature.com/reprints. Additional informationSupplementary information and chemical compound information are available in the online version of the paper. Competing financial interestsThe authors declare no competing interests. forming reaction with the C 3 sugar glyceraldehyde 4 giving rise to a mixture of pentose aminooxazolines. Reaction of the arabino-configured aminooxazoline 5 with cyanoacetylene 6 then furnishes an anhydronucleoside 7 which on heating with phosphate in urea 8 -a by-product of the first step of the sequence -is transformed into ribo-cytidine-2′, 3′-cyclic phosphate 9. UV irradiation then partially converts this nucleotide into uridine-2′, 3′-cyclic phosphate 10 and destroys stereoisomeric impurities. Europe PMC Funders GroupWe subsequently showed that the C 2 and C 3 sugars, 1 and 4, can be sequentially provided by a Kiliani-Fischer-type homologation of hydrogen cyanide 11 using Cu(I)-Cu(II) photoredox chemistry (Fig. 1a, bold, green arrows) 8,9 . Using hydrogen sulfide 12 as the stoichiometric reductant -in which case the inclusion o...

A recent synthesis of activated pyrimidine ribonucleotides under prebiotically plausible conditions relied on mixed oxygenous and nitrogenous systems chemistry. As it stands, this synthesis provides support for the involvement of RNA in the origin of life, but such support would be considerably strengthened if the sugar building blocks for the synthesis--glycolaldehyde and glyceraldehyde--could be shown to derive from one carbon feedstock molecules using similarly mixed oxygenous and nitrogenous systems chemistry. Here, we show that these sugars can be formed from hydrogen cyanide by ultraviolet irradiation in the presence of cyanometallates in a remarkable systems chemistry process. Using copper cyanide complexes, the process operates catalytically to disproportionate hydrogen cyanide, first generating the sugars and then sequestering them as simple derivatives.

On their own, neither sulfite nor ferrocyanide are efficient sources of photochemically-generated electrons for the reductive homologation of hydrogen cyanide, but together they are.

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When considering life’s aetiology, the first questions that must be addressed are “how?” and “where?” were ostensibly complex molecules, considered necessary for life’s beginning, constructed from simpler, more abundant feedstock molecules on primitive Earth. Previously, we have used multiple clues from the prebiotic synthetic requirements of (proto)biomolecules to pinpoint a set of closely related geochemical scenarios that are suggestive of flow and semi-batch chemistries. We now wish to report a multistep, uninterrupted synthesis of a key heterocycle (2-aminooxazole) en route to activated nucleotides starting from highly plausible, prebiotic feedstock molecules under conditions which mimic this scenario. Further consideration of the scenario has uncovered additional pertinent and novel aspects of prebiotic chemistry, which greatly enhance the efficiency and plausibility of the synthesis.