Prebiotic peptide formation triggered by urea-rich warm little ponds on early earth

In the study of the origin of life, the polymerization of amino acids into peptides in water faces significant thermodynamic barriers, often referred to as the "water problem." It has been demonstrated that the reaction between urea and amino acids can efficiently yield carbamoyl amino acids (CAAs); however, whether urea and amino acids can polymerize into peptides through early geochemical reactions remains unclear. This study demonstrates that urea and amino acids at equivalent concentrations can polymerize into peptides under mild alkaline conditions (65 °C, pH 9.0). Subsequent mechanistic studies reveal that this reaction can be divided into two steps: the first step the reaction between urea and amino acids to form carbamoyl amino acids; the second step the N-terminal extension of the carbamoyl amino acid to generate N-carboxyl anhydrides (NCAs), followed by their polymerization with amino acids to form peptides; and the C-terminal extension leads to the formation of 2-amino-5(4H)-oxazolidinone, which then polymerizes with amino acids to form carbamoyl peptides. This bidirectional growth mechanism has been verified across 20 proteinogenic amino acids, with peptides as the major reaction products and carbamoyl peptides as the minor products. Our findings indicate that the "warm small ponds" of the early Earth were not only reservoirs for organic precursor substances but also "active reactors" for early geochemical reactions, driving the pre-biological synthesis of complex biomolecules.