Biomolecular condensates formed by intrinsically disordered proteins possess inherent catalytic activities that emerge from their sequence-dependent electrochemical microenvironments and interfacial electric fields, enabling them to function as programmable mesoscale catalysts ("condenzymes") that can hydrolyze diverse cellular substrates including complete ATP decomposition to adenine, with catalytic behaviors controllable through rational sequence design and functional in living cells where they modulate ATP levels, activate transcription pathways, and drive synthetic gene circuits.

We report the discovery that chemical reactions can be catalyzed by condensates formed by intrinsically disordered proteins (IDPs). The proteins themselves lack any catalytic activities. Catalytic functions of condensates emerge as a consequence of sequence-dependent mesoscale electrochemical microenvironments created by phase separation. Stimulated Raman spectroscopy suggests that the catalytic behaviors of condensates are attributable to the spatial variations of water activities across condensate interiors and interfaces. We show that condensates are capable of catalyzing diverse cellularly relevant hydrolysis reactions. Through sequence design, the electrochemical properties of condensates can be programmed to exert control over catalytic behaviors. Incorporation of synthetic condensates into live cells alters transcription profiles and enables the activation of gene circuits that depend on products of hydrolysis reactions catalyzed by condensates. Our discovery of suggests that condensates, depending on their composition-dependent electrochemical properties, can be “Condenzymes”, which contribute unexpected emergent chemical functions in cells.