Hierarchically Porous Biocatalytic MOF Microreactor as a Versatile Platform towards Enhanced Multienzyme and Cofactor‐Dependent Biocatalysis

Metal‐organic frameworks (MOFs) have recently emerged as excellent hosting matrices for enzyme immobilization, offering superior physical and chemical protection for biocatalytic reactions. However, for multienzyme and cofactor‐dependent biocatalysis, the subtle orchestration of enzymes and cofactors is largely disrupted upon immobilizing in the rigid crystalline MOF network, which leads to a much reduced biocatalytic efficiency. Herein, we constructed hierarchically porous MOFs by controlled structural etching to enhance multienzyme and cofactor‐dependent enzyme biocatalysis. The expanded size of the pores can provide sufficient space for accommodated enzymes to reorientate and spread within MOFs in their lower surface energy state as well as to decrease the inherent barriers to accelerate the diffusion rate of reactants and intermediates. Moreover, the developed hierarchically porous MOFs demonstrated outstanding tolerance to inhospitable surroundings and recyclability. Hierarchically porous biocatalytic MOFs provide sufficient space for accommodation of enzymes to reorientate and spread in their lower surface energy state as well as to decrease the inherent barriers to accelerate the diffusion of reactants and intermediates. The promoted intermolecular correlation of enzymes and MOFs, and polyphenol coating, safeguards the enzymes from inactivation, showcasing their promise for diverse biotechnological applications.