Search

Compartmentalization protected biomolecules from the fluctuating environments of early Earth. Although contemporary cells mostly use phospholipid‐based bilayer membranes, the utility of non‐bilayer compartments was not ruled out during the prebiotic and modern eras. In the present study, we demonstrated the prebiotic synthesis of lipidated cationic amino acid‐based amphiphiles [lauryl ester of lysine (LysL); ornithine (OrnL); and 2,4‐diamino butyric acid (DabL)] using model dry‐down reaction. These amphiphiles self‐assemble into micellar membranes. However, the OrnL and DabL‐based micelles undergo pH‐responsive transformation to lipid droplet‐like morphologies, a modelcompartment in the prebiotic Earth. These cationic droplets encapsulated prebiotic molecules (isoprene) and assisted electron transfer reaction to synthesize isoprenoid derivatives at primitive Earth conditions. The self‐assembly of prebiotic amphiphiles, their transformation to droplet compartments, and droplet‐assisted C−C bond formation reaction might have helped the evolution to synthesize various biomolecules required for the origin of life. [ABSTRACT FROM AUTHOR]

The proteinogenic lysine (Lys) and arginine (Arg) have multiple methylene groups between α-carbon and the terminal charged centre. Why nature did not select ornithine (Orn), 2,4-diamino butyric acid (Dab) and 2,3-diamino propionic acid (Dpr) with fewer methylene groups in the side chain remains an important question! The propensity of aminoacyl-tRNA (aa-tRNA) model substrates towards self-degradation via intramolecular lactamization was studied using UV spectroscopy and 1 H-NMR titration, which showed that Lys and Arg remain stable, and Orn and Dab cyclize to lactam. Hydrophobicity-assisted surface mediated model peptide formation highlighted that the microenvironment and p K a perturbation led to poor regioselectivity (α-amine vs. terminal amine) in Dpr and other non-proteinogenic analogues. The α-selectivity became even poorer in the presence of phosphate, making them ill-suited for peptide synthesis. Superior regioselectivity of the Lys aa-tRNA model substrate suggests that the extra methylene bridge helped nature to separate the microenvironments of the α-amine and ε-amine to synthesize the peptide backbone.