Elucidating N-acyl amino acids as a model protoamphiphilic system

Protoamphiphiles are prebiotically-plausible moieties that would have constituted protocell membranes on early Earth. Although prebiotic soup would have contained a diverse set of amphiphiles capable of generating protocell membranes, earlier studies were mainly limited to fatty acid-based systems. Herein, we characterize N-acyl amino acids (NAAs) as a model protoamphiphilic system. Specifically, we report a new abiotic route for their synthesis under wet-dry cycles from amino acids and monoglycerides via an ester-amide exchange process. We also demonstrate how N-oleoyl glycine (NOG, a representative NAA) results in vesicle formation over a broad pH range when blended with a monoglyceride or a fatty acid. Notably, NOG also acts as a substrate for peptide synthesis under wet-dry cycles, generating different lipopeptides. Overall, our study establishes NAAs as a promising protoamphiphilic system, and highlights their significance in generating robust and functional protocell membranes on primitive Earth.