Stereoselective peptide synthesis in alkaline hydrothermal vent conditions

Modern proteins are composed exclusively of L-amino acids but the origin of L-stereospecificity is unresolved. Carbonaceous meteorites were a significant source of organic matter on early Earth and commonly contain ten proteogenic amino acids in racemic mixtures. In conditions relevant to early Earth hydrothermal vents, surface-catalyzed peptide syntheses of these proteogenic mixtures show modest reaction rates and no significant stereoselectivity. However, we show that the presence of cysteine significantly increases peptide synthesis yields in the presence of silicate surfaces, with synthetic yields displaying a strong stereoselective bias towards L-cysteine. In a hydrothermal vent solvent model, L-cysteine doubles the increase in peptide synthetic yields compared to D-cysteine, as indicated by UV absorption, NMR, and mass spectrometry. Solid state NMR confirms that cysteine associates with silicates at alkaline pH via both carboxylate and sulfur groups. This adsorption results in a stereospecific orientation of the reactive amino group for surface-adsorbed bivalently charged amino acids detectable by Polarization-Resolved IRRAS. This stereospecific amino group reorientation provides a novel mechanism for abiotic peptide synthesis favoring L-amino acids on achiral surfaces, which is applicable to any bivalently charged amino acid at alkaline pH. Our findings here, that cysteine is incorporated stereoselectively in surface-catalyzed peptide synthesis, combined with the metal-binding capability of abiotically synthesized cysteine-bearing peptides, emphasizes the potential benefits of amino acids with sulfur functional groups to fundamental processes in early life and the potential usefulness of such amino acids as biosignatures.