Selective amide bond formation in redox-active coacervate protocells

Membraneless compartments, like complex coacervates droplets, are promising protocell models because of their ability to sequester a wide range of guest molecules and their catalytic properties. However, it remains unclear how the building blocks of life, including peptides, could be synthesized from primitive precursor molecules inside such protocells. Here, we develop a new protocell model formed by phase separation of prebiotically relevant small redox-active ferricyanide (Fe(CN)_6^{3−})/ferrocyanide (Fe(CN)_6^{4−}) molecules and a cationic peptide. The assembly of these coacervate protocells can be regulated by redox chemistry and they act as oxidizing hubs for sequestered metabolites, such as NAD(P)H, and fiber precursors. Interestingly, we show that the oxidizing potential of ferricyanide inside coacervates can be harnessed to drive the selective formation of amide bonds between prebiotically relevant amino thioacids and amino acids or peptides. We demonstrate that aminoacylation is enhanced in Fe(CN)_6^{3−}/peptide coacervate dispersions compared to the surrounding dilute phase, and selective for amino acids that interact less strongly with the coacervates. We finally use this amide bond formation to create self-reinforcing coacervates by reacting hydrophobic amino thioacids to amines on the protocell scaffold and show that this significantly enhances their salt resistance. These results provide an important step towards the prebiotically relevant integration of redox chemistry in cell-like compartments.