Dynamic and Catalytic Multiphase Coacervates

Abstract Catalytic reactions in multiphase coacervate systems are important for living cells, provide functionality to artificial systems, and may aid in understanding how metabolism first arose, but are not yet well understood. Here, we report an artificial multiphase system in which catalytically active droplets containing three phases undergo reorganization in response to pH, enabling control over chemical reactions. Catalysis is performed by an inner, polyhistidine-dense coacervate phase with inherent nonenzymatic activity, and the multiphase architecture stabilizes this otherwise aggregation-prone component against precipitation. We show that phase hierarchy provides catalytic design degrees of freedom fundamentally inaccessible in single-phase systems, including spatial decoupling of catalyst, substrate, and product that significantly enhances reaction rates, and that phase reorganization itself can be catalytically productive. By exploiting competitive interplay between intra- and intermolecular interactions between components, it was possible to (re)organize and tune the reactivity of dynamic synthetic biological systems in ways unavailable to single-phase coacervates.