Nonenzymatic Carboxylate Phosphorylation in Water

The core pathways of autotrophic microbial metabolism have been proposed to be fossils of self-organized prebiotic chemistry. In recent years, numerous reactions within these pathways have been shown to occur nonenzymatically, supporting this hypothesis. However, the phosphorylation of carboxylic acids to the corresponding acyl phosphates, a recurring metabolic reaction, has yet to be demonstrated without enzymes. Here we show that carboxylate phosphorylation is promoted by diamidophosphate (DAP) and sodium nitrite in the presence of water, driven by the release of dinitrogen. The reaction occurs in minutes at 0-50 °C to convert carboxylic acids to acyl amidophosphate intermediates, which then undergo nitrite-promoted hydrolysis to give the corresponding acyl phosphates. Though we do not claim the conditions used here were directly relevant to the origin of life, the observation of aqueous nonenzymatic carboxylate phosphorylation to simple acyl phosphates in the absence of adenosine triphosphate (ATP) raises the enticing prospect that it might also be achieved using driving forces more congruent with the principles of cellular bioenergetics.