Complex Coacervation and Compartmentalized Conversion of Prebiotically Relevant Metabolites**

Abstract

Abstract 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 can form complex coacervate protocells with oligoarginine (R 10 ) by phase separation. The coacervate stability 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 moiety for phosphates and sulfates is sufficient for phase separation. The metabolites remain reactive after compartmentalization, and we show that protometabolic reactions can induce coacervate formation. 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. These results reveal the intricate interplay between (proto)metabolic reactions and coacervate compartments, and show that coacervates are excellent candidates for metabolically active protocells.