Screening of Protein‐Based Ultrasmall Nanozymes for Building Cell‐Mimicking Catalytic Vesicles

Abstract Enzymes are an important component for bottom‐up building of synthetic/artificial cells. Nanozymes are nanomaterials with intrinsic enzyme‐like properties, however, the construction of synthetic cells using nanozymes is difficult owing to their high surface energy or large size. Herein, the authors show a protein‐based general platform that biomimetically integrates various ultrasmall metal nanozymes into protein shells. Specifically, eight metal‐based ultrasmall nano‐particles/clusters are in situ incorporated into ferritin nanocages that are self‐assembled by 24 subunits of ferritin heavy chain. As a nanozyme generator, such a platform is suitable for screening the desired enzyme‐like activities, including peroxidase (POD), oxidase (OXD), catalase (CAT) and superoxide dismutase (SOD). After screening, it is found that Ru intrinsically possesses the highest POD‐like and CAT‐like activities, while Mn and Pt show the highest OXD‐like and SOD‐like activities, respectively. Additionally, the inducers/inhibitors of various nanozymes are screened from more than 50 compounds to improve or inhibit their enzyme‐like activities. Based on the screened nanozymes and their inhibitors, a proof‐of‐conceptually constructs cell‐mimicking catalytic vesicles to mimic or modulate the events of redox homeostasis in living cells. This study offers a type of artificial metalloenzyme based on nanotechnology and shows a choice for bottom‐up enzyme‐based synthetic cell systems in a fully synthetic manner.