Condenzymes: Biomolecular condensates with inherent catalytic activities

Kavli Affiliate: Wei Min

| Authors: Michael W Chen, Xiao Guo, Mina Farag, Naixin Qian, Xiaowei Song, Anton Ni, Vicky Liu, Xia Yu, Yuefeng Ma, Leshan Yang, Wen Yu, Matthew King, Joonho Lee, Richard N Zare, Wei Min, Rohit V Pappu and Yifan Dai

| Summary:

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.

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