Complex coacervation and compartmentalized conversion of prebiotically relevant metabolites

Metabolism and compartmentalization are two of life’s most central elements. Constructing synthetic assemblies based on prebiotically relevant molecules that combine these elements can provide insight into the requirements for the formation of life-like protocells from abiotic building blocks. In this work, we show that a wide variety of small anionic metabolites have strong enough interactions with oligoarginine (R10) to form coacervate protocells through liquid-liquid phase separation. The stability of the coacervates can be rationalized by the molecular structure of the metabolites, and we show that three negative charges for carboxylates or two negative charges complemented with an unsaturated functional group for phosphates and sulfates is sufficient for phase separation. We show that these metabolites remain reactive in compartmentalized systems. Protometabolic reactions that lead to an increased interaction with the oligopeptide can be exploited to induce the formation of coacervate protocells. The resulting coacervates can localize other metabolites and enhance their conversion. Finally, reactions of compartmentalized metabolites can also alter the physicochemical properties of the coacervates and ultimately lead to protocell dissolution if the reaction products decrease the coacervate stability. These results reveal the intricate interplay between (proto)metabolic reactions and coacervate compartments, and show that coacervates are excellent candidates for metabolically active protocells.