At some stage in the origin of life, an informational polymer must have arisen by purely chemical means. According to one version of the 'RNA world' hypothesis this polymer was RNA, but attempts to provide experimental support for this have failed. In particular, although there has been some success demonstrating that 'activated' ribonucleotides can polymerize to form RNA, it is far from obvious how such ribonucleotides could have formed from their constituent parts (ribose and nucleobases). Ribose is difficult to form selectively, and the addition of nucleobases to ribose is inefficient in the case of purines and does not occur at all in the case of the canonical pyrimidines. Here we show that activated pyrimidine ribonucleotides can be formed in a short sequence that bypasses free ribose and the nucleobases, and instead proceeds through arabinose amino-oxazoline and anhydronucleoside intermediates. The starting materials for the synthesis-cyanamide, cyanoacetylene, glycolaldehyde, glyceraldehyde and inorganic phosphate-are plausible prebiotic feedstock molecules, and the conditions of the synthesis are consistent with potential early-Earth geochemical models. Although inorganic phosphate is only incorporated into the nucleotides at a late stage of the sequence, its presence from the start is essential as it controls three reactions in the earlier stages by acting as a general acid/base catalyst, a nucleophilic catalyst, a pH buffer and a chemical buffer. For prebiotic reaction sequences, our results highlight the importance of working with mixed chemical systems in which reactants for a particular reaction step can also control other steps.

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...

Either to sustain autotrophy, or as a prelude to heterotrophy, organic synthesis from an environmentally available C1 feedstock molecule is crucial to the origin of life. Recent findings augment key literature results and suggest that hydrogen cyanide--"Blausäure"--was that feedstock.

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.

Researchers identify an “abiogenesis zone,” outside of which the building blocks of life cannot form photochemically.