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. 2015 Apr;7(4):301-7.
doi: 10.1038/nchem.2202. Epub 2015 Mar 16.

Common Origins of RNA, Protein and Lipid Precursors in a Cyanosulfidic Protometabolism

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Common Origins of RNA, Protein and Lipid Precursors in a Cyanosulfidic Protometabolism

Bhavesh H Patel et al. Nat Chem. .
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A minimal cell can be thought of as comprising informational, compartment-forming and metabolic subsystems. To imagine 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 experimentally investigate 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 the 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 ultraviolet light, use hydrogen sulfide as the reductant and can be accelerated by Cu(I)-Cu(II) photoredox cycling.


Figure 1
Figure 1. Reaction network leading to RNA, protein and lipid precursors
The degree to which syntheses of ribonucleotides and amino acid and lipid precursors are interconnected is apparent in this ‘big picture’. The network does not produce a plethora of other compounds, however, suggesting that biology did not select all of its building blocks, but was simply presented with a specific set as a consequence of the (photo)chemistry of hydrogen cyanide 11 and hydrogen sulfide 12, and that set turned out to work. To facilitate description of the chemistry in the text, the picture is divided into four parts. a. Reductive homologation of hydrogen cyanide 11 (bold green arrows) provides the C2 and C3 sugars – glycolaldehyde 1 and glyceraldehyde 4 – needed for subsequent ribonucleotide assembly (bold blue arrows), but also leads to precursors of Gly, Ala, Ser and Thr. b. Reduction of dihydroxyacetone 17 – the more stable isomer of glyceraldehyde 4 – gives two major products acetone 18 and glycerol 19. Reductive homologation of acetone 18 leads to precursors of Val and Leu whilst phosphorylation of glycerol 19 leads to the lipid precursor glycerol-1-phosphate 21. c. Copper(I) catalysed cross-coupling of hydrogen cyanide 11 and acetylene 32 gives acrylonitrile 33, reductive homologation of which gives precursors of Pro and Arg. d. Copper(II) driven oxidative cross-coupling of hydrogen cyanide 11 and acetylene 32 gives cyanoacetylene 6 which serves as a precursor to Asn, Asp, Gln and Glu.
Figure 2
Figure 2. Chemistry in a post meteoritic impact scenario
A series of post impact environmental events are shown along with chemistry (boxed) proposed to occur as a consequence of those events. a. Dissolution of atmospherically produced hydrogen cyanide results in conversion of vivianite – the anoxic corrosion product of the meteoritic inclusion schreibersite – into mixed ferrocyanide salts and phosphate salts, counter cations being provided through neutralisation and ion-exchange reactions with bedrock and other meteoritic oxides and salts. b. Partial evaporation results in the deposition of the least soluble salts over a wide area, further evaporation deposits the most soluble salts in smaller, lower lying areas. c. After complete evaporation, impact or geothermal heating results in thermal metamorphosis of the evaporite layer, and generation of feedstock precursor salts. d. Upper. Rainfall on higher ground leads to rivulets or streams that flow downhill sequentially leaching feedstocks from the thermally metamorphosed evaporite layer. Solar irradiation drives photoredox chemistry in the streams. Lower. Convergent synthesis can result when streams with different reaction histories merge, as illustrated here for the potential synthesis of arabinose aminooxazoline 5 at the confluence of two streams that contained glycolaldehyde 1, and leached different feedstocks before merging.

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