Transmembrane Activation of Catalysis and Protein Refolding in Synthetic Cells by Enzymes and Nanozymes

Abstract The design of artificial cells is a focal point of intense research efforts. One characteristic that remains particularly hard to engineer is the responsive behavior in artificial cells. It requires the design of molecular mechanisms to receive, interpret, and react to external environmental or biochemical stimuli. This challenge is specifically addressed herein and the design of artificial cells that respond to the external chemical messenger by the activation of intracellular catalysis is presented. Chemistry of thiols is used as the unifying platform for the generation of chemical messenger molecules in the extracellular space, for the activation of catalysis in the enzymes via “thiol switching”, and for protein refolding. The chemical messenger molecules are catalytically generated by the extracellular enzymes or the mineral surfaces with inherent catalytic activity. Specific points of novelty of this work include the selection of the lead compound for transmembrane communication and the on‐demand protein refolding within the confines of synthetic cells. Most importantly, the activation of catalysis in artificial cells is demonstrated by both, biochemical factors and the abiotic, environmental cues. The results of this study make an important step toward the realization of life‐like responsive behavior in abiotic, artificial cells.