Solvent‐ and Energy‐Free Solid‐State Strategy for Enzyme Encapsulation in ZIF

Conventional enzymes immobilization strategies within metal–organic frameworks (MOF) typically require solvents and energy, resulting in solvent residues, environmental pollution, and high energy consumption. In this work, we present a solvent‐ and energy‐free solid‐state strategy for synthesizing enzyme‐zeolitic imidazolate framework (ZIF) biocomposites. The nucleation of enzyme‐ZIF is driven by acid–base interactions through the directly mixing of enzymes with ZIF precursors. The resulting biocomposites exhibit up to a four‐fold enhancement in enzymatic activity compared to liquid‐phase methods and a 1000‐fold increase compared to free enzymes. This enhancement is attributed to the ZIF's multiphase crystalline structure, larger pore size, significantly higher surface area, and greater total pore volume, as well as a more favorable enzyme conformation (e.g., an open active‐site pocket) achieved during synthesis followed by immobilization. Additionally, the synthesized enzyme‐ZIF composites display excellent stability against organic solvents, proteolytic enzymes, and high temperatures, along with outstanding recyclability. This simple and sustainable approach to biocatalytic ZIF synthesis paves the way for the development of green, efficient, and robust biocatalysts for industrial applications.