Spontaneous emergence of membrane-forming protoamphiphiles from a lipid-amino acid mixture under wet-dry cycles.

Dynamic interplay between peptide synthesis and membrane assembly would have been crucial for the emergence of protocells on the prebiotic Earth. However, the effect of membrane-forming amphiphiles on peptide synthesis, under prebiotically plausible conditions, remains relatively unexplored. Here we discern the effect of a phospholipid on peptide synthesis using a non-activated amino acid, under wet-dry cycles. We report two competing processes simultaneously forming peptides and N-acyl amino acids (NAAs) in a single-pot reaction from a common set of reactants. NAA synthesis occurs via an ester-amide exchange, which is the first demonstration of this phenomenon in a lipid-amino acid system. Furthermore, NAAs self-assemble into vesicles at acidic pH, signifying their ability to form protocellular membranes under acidic geothermal conditions. Our work highlights the importance of exploring the co-evolutionary interactions between membrane assembly and peptide synthesis, having implications for the emergence of hitherto uncharacterized compounds of unknown prebiotic relevance.