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 notably yet to be demonstrated without enzymes. Here, this study shows that carboxylate phosphorylation is promoted by diamidophosphate 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. The partial overlap in scope with important metabolic carboxylates and the concentrated acidic conditions likely limit its direct applicability in metabolic origins of life scenarios. Nonetheless, the work represents a step forward in understanding nonenzymatic carboxylate phosphorylation and helps clarify how the transformation might eventually be rendered compatible with a protometabolism.