Cyanide as a primordial reductant enables a protometabolic reductive glyoxylate pathway

Investigation of prebiotic metabolic pathways is predominantly based on abiotically replicating the reductive citric acid cycle. While attractive from a parsimony point of view, attempts using metal/mineral-mediated reductions have produced complex mixtures with inefficient and uncontrolled reactions. Here we show that cyanide acts as a mild and efficient reducing agent mediating abiotic transformations of tricarboxylic acid intermediates and derivatives. The hydrolysis of the cyanide adducts followed by their decarboxylation enables the reduction of oxaloacetate to malate and of fumarate to succinate, whereas pyruvate and alpha-ketoglutarate themselves are not reduced. In the presence of glyoxylate, malonate and malononitrile, alternative pathways emerge that bypass the challenging reductive carboxylation steps to produce metabolic intermediates and compounds found in meteorites. These results suggest a simpler prebiotic forerunner of today's metabolism, involving a reductive glyoxylate pathway without oxaloacetate and alpha-ketoglutarate-implying that the extant metabolic reductive carboxylation chemistries are an evolutionary invention mediated by complex metalloproteins.

Automated summary

The study reveals that cyanide acts as a mild and efficient reducing agent in mediating abiotic transformations of tricarboxylic acid intermediates and derivatives. The results suggest the existence of a simpler prebiotic metabolic pathway, bypassing the challenging reductive carboxylation steps.