PhosphorusChemistry and the Origin of Life: From N -PhosphorylAmino Acid to Protocell

Conspectus A central question in origin-of-life research is how biological macromolecules and cellular structures arose from simple precursors under prebiotic conditions. This review focuses on the chemical evolution model of N-phosphoryl amino acids (NPAAs) and their multifaceted roles in this process. Featuring high-energy P–N bonds, NPAAs enable intramolecular activation via pentacoordinate phosphorus intermediates, facilitating the formation of homochiral peptides and nucleotides under mild aqueous conditions. Moreover, N-amino acid-nucleotide conjugates (N-aa-NMPs) drive peptide formation with chiral selection between amino acids and nucleosides, where the peptide yield for each amino acid is modulated by specific nucleosides, thereby laying a foundation for a proto-genetic code. Additionally, amphiphilic NPAA derivatives spontaneously self-assemble into vesicles and selectively condense peptides at membrane interfaces, whereas the in situ generation of N-fatty acyl amino acids further enhances membrane stability. Collectively, these findings support a phosphorus-centered model for the integrated origin of nucleic acids, proteins, and membranes.