Catalytically Active Coacervates Sustained Out‐of‐Equilibrium

Metabolically active membraneless organelles of extant biology have the capability to maintain their structure under nonequilibrium conditions by leveraging chemical reactions. Herein, we report active coacervates accessed via a mixture of minimal building blocks that featured π-electron rich short peptide, positively charged aldehyde, and a cyclic ketone under nonequilibrium conditions. Peptide bound with the aldehyde by a dynamic covalent bond and demixed to form coacervates through hydrophobic interactions. Importantly, the short-peptide could utilize its free amine (β-alanine) to catalyze C─C bond formation which eventually led to the depletion of one of the building blocks (aldehyde) via aldol reaction; an intrinsic catalytic role that helped the coacervate to suppress coalescence. Notably, under continuous additions (open system) of the depleting precursors, the active coacervates were able to demonstrate spatial stability for longer duration. This out-of-equilibrium behavior of phase separated droplets in presence of flux of building blocks is reminiscent of the active membraneless organelles seen in contemporary biochemistry.