Multi‐Subunit Nanozyme: A Functionally Programmed Ru Nanocluster‐Installed Tannic Acid‐Framed Hollow ZIF‐8 Single Construct Exhibits Subunit‐Specific Roles in Facilitating Remarkable Substrate Selective Catalysis

ABSTRACT Multi‐subunit enzymes are constituted with multiple domains defined for specific functions for efficient biocatalysis. Replicating complex features and functions of multi‐subunit enzymes in nanozymes remains unexplored and warrants investigation to advance nanozyme technology. However, the formidable challenge is to architect multiple subunits in a single nanozyme construct. Herein, we introduce a new concept of multi‐subunit nanozyme (Ru‐H‐ZIF‐8) by installing Ru nanoclusters (Ru‐NCs) as a catalytic subunit on a structural/regulatory subunit, tannic acid (TA)‐framed hollow ZIF‐8 (H‐ZIF‐8). These subunits in a single nanozyme construct perform defined yet synergistic roles for mimicking multi‐subunit enzymes. The TA‐bound Ru‐H‐ZIF‐8 nanozyme activates o ‐aminophenol (OAP) via hydrogen bonding, while the Ru‐NCs subunit facilitates electron transfer to catalyse oxidation, collectively exhibiting a high reaction rate with remarkable substrate class selectivity, which is otherwise difficult to achieve by individual components. This nanozyme class significantly differs from typical non‐selective oxidase mimetics. The Ru‐H‐ZIF‐8 nanozyme parallelly completes four‐electron oxygen reduction without releasing partially reduced oxygen species (PROS), and enzyme‐like specificity comparable only to phenoxazinone synthase (PHS). Supported by detailed mechanistic insights, our investigation establishes a new functionally programmed multi‐subunit nanozyme, advancing nanozyme research by constructing a dynamic bioinspired catalytic system having multi‐subunits with specific functions.