Catalysis-Induced Phase Separation and Autoregulation of Enzymatic Activity

Liquid-liquid phase separation is an exciting feature of subcellular organisation believed to be vital to the formation of membraneless organelles. It is generally believed that the main drivers of phase separation in such systems are attractive equilibrium interactions which are needed to overcome the entropic costs associated with phase separation. However, we present a thermodynamically consistent model describing the dynamics of a multi-component mixture where one enzyme component catalyzes a reaction between other components. We find that the catalytic activity alone can induce phase separation for sufficiently active systems and large enzymes, without any equilibrium interactions between components. In the limit of fast reaction rates, binodal lines can be calculated using a mapping to an effective free energy. When this catalysis-induced phase separation occurs, the overall catalytic rate in the system is reduced and as such this automatically regulates the enzymatic activity. This points to the biological relevance of this phenomenon and how this effect could be used in synthetic systems.