Generation of Protocells by Spontaneous Reaction of Cysteine with Short Chain Thioesters

It is unknown how the earliest forms of life were compartmentalized. Several models have suggested a role for single-chain lipids such as fatty acids, but the membranes formed are often unstable, particularly when made from shorter alkyl chains (≤C8) that were likely more prevalent on the prebiotic Earth. We show that the amino acid cysteine can spontaneously react with two short-chain (C8) thioesters to form diacyl lipids, generating protocell-like membrane vesicles. The three-component reaction takes place rapidly in water using low concentrations of reactants. Silica can catalyze the formation of protocells through a simple electrostatic mechanism. Several simple aminothiols react to form diacyl lipids, including short peptides. The protocells formed are compatible with functional ribozymes, suggesting that coupling of multiple short-chain precursors may have provided membrane building blocks during the early evolution of cells.