Carbamoyl phosphate-mediated peptide formation in mild prebiotic environment

Abstract The abiotic formation of peptides in water remains a fundamental challenge in origin-of-life research. Direct aqueous condensation of amino acids is thermodynamically hindered; consequently, existing models frequently depend on activation agents or require extreme conditions. We have developed and implemented an aqueous pathway for peptide synthesis mediated by carbamoyl phosphate (CAP) within a mild, “warm little pond” scenario. Co-incubation of diverse proteinogenic amino acids with CAP and metal cations promoted peptide bond formation. Our analysis reveals that magnesium ions operate synergistically with CAP, driving a dual-activation mechanism through N -carbamoylation and O -phosphorylation intermediates. Crucially, we establish that CAP can be generated in situ directly from early-Earth accessible precursors, urea and orthophosphate. This continuous aqueous pathway entirely bypasses the necessity for destructive dry-state cycles. CAP continues to play a vital role in nitrogen metabolism and the de novo synthesis of pyrimidine nucleotides in extant organisms. Therefore, we suggest that CAP serves as an evolutionary bridge, linking primordial geochemical conditions to the emergence of functional biochemical machinery.