Acyl Phosphate‐Driven Acylation in Biology, Chemistry, and in Between

ABSTRACT Acyl phosphates are high‐energy intermediates that play a central role in acyl transfer reactions throughout biology. The phosphate‐mediated activation of carboxylic acids as mixed anhydrides underpins most acylation‐based processes, such as aminoacyl‐tRNA formation in translation or post‐translational modifications. In cells, these transformations are tightly controlled by enzymatic machineries. In contrast, abiotic chemical reaction networks allow the intrinsic reactivity and selectivity of acyl phosphates to be dissected and repurposed. This review highlights the emerging potential of acyl phosphates in chemical biology, systems chemistry and origins‐of‐life research, seeking to connect their biological and synthetic functions. We discuss their synthesis and reactions across prebiotic, abiotic and biotic settings, focusing on recent advances using (amino)acyl phosphates in chemically fueled reaction cycles and peptide synthesis. Here, acyl transfer is coupled to supramolecular organization and non‐equilibrium behavior, paralleling biological strategies like confinement and energetic coupling. Acyl phosphates may thus bridge the gap between biology and chemistry, offering a particularly suitable means to link mechanisms from nature to fully synthetic systems that emulate, extend, or diverge from them.