Biomolecular condensates can function as inherent catalysts

Biomolecular condensates possess distinct solvent environments. This has been postulated to affect biochemical activities. Here, we report the discovery of inherent catalytic functions of condensates formed by intrinsically disordered proteins. The proteins themselves lack any catalytic activities. The catalytic functions of condensates emerge as a consequence of phase separation-dependent mesoscale electrochemical microenvironments. Condensates can mediate the hydrolysis of diverse types of biologically relevant substrates. Through sequence design that enriches selective residues at condensate interfaces, interfacial electrochemical properties, such as interfacial electric field and water activity, are shown to control catalytic behaviors. Synthetic condensates in live cells exhibit hydrolytic activity, reshaping transcription profiles and activating gene circuits that depend on hydrolytic products. Together, these findings support a model that biomolecular condensates function as "condenzymes," contributing emergent biochemical functions in cells.