PEPREP · Peptide based self-replicating coacervate protocells

One of the most fundamental questions in chemistry and biology is how a self-replicating protocell could form from collection of inanimate molecules. Self-replicating RNA molecules in lipid compartments have been widely studied, but these systems are inherently unstable and a plausible mechanism for their spontaneous formation and repeated replication is still lacking. Here, I propose to use coacervation of self-templating peptides as a radically new approach to create stable self-replicating protocells. We will use short peptide building blocks with aromatic and ionic side chains that are designed for self- or cross-recognition. The building blocks can dimerize through reversible or irreversible chemical bond formation, including disulfide, imine, alkene (metathesis) and peptide (native chemical ligation) bonds. Preliminary results indicate that these peptides spontaneously form coacervate droplets when dimerized. The coacervates enhance the self-replication by naturally concentrating the peptide building blocks, catalyzing the template-directed peptide dimerization and stabilizing the product. By periodic cycling of the solution temperature or pH, the coacervate protocells can be dissolved and recondensed, yielding an elementary system of self-replicating protocells. These coacervate protocells not only concentrate peptides, but also nucleotides, inorganic nanoparticles and pigments, creating a potent microreactor for prebiotic chemistry. Developing these model system will provide valuable insights in new prebiotically plausible pathways to self-replication and the origin of life.