Regulation of enzymatic reactions by chemical composition of peptide biomolecular condensates

Abstract Biomolecular condensates are condensed intracellular phases that are formed by liquid-liquid phase separation (LLPS) of proteins, either in the absence or presence of nucleic acids. These condensed phases regulate various biochemical reactions by recruitment of enzymes and substrates. Developments in the field of LLPS facilitated new insights on the regulation of compartmentalized enzymatic reactions. Yet, the influence of condensate chemical composition on enzymatic reactions is still poorly understood. Here, by using peptides as minimalistic condensate building blocks and β-galactosidase as a simple enzymatic model we show that the reaction is restricted in homotypic peptide condensates, while product formation is enhanced in peptide-RNA condensates. Our findings also show that condensate composition affects the recruitment of substrate, the spatial distribution, and the kinetics of the reaction. Thus, these findings can be further employed for the development of microreactors for biotechnological applications.