Unveiling the Critical Role of Spatial Organization on Enzymatic Cascade Reactions in a Crystalline Framework with Hierarchical Porosity

Abstract

Enzymatic cascades are critical for energy conversion and chemical transformations in living organisms. Their ecofriendly nature and high selectivity in catalysis make them promising candidates for improving chemical transformations in cell-free systems. However, their applications have been limited by their poor stability. Immobilized cascades, which can enhance activity, remain underexplored due to challenges such as ambiguous support structures and difficulties in controlling enzyme distribution. In this work, we employed NU-1510, a novel metal–organic framework (MOF) with a crystalline hierarchical pore structure, to stabilize an enzyme cascade that oxidizes ethanol to acetaldehyde and subsequently to acetic acid. The impact of enzyme spatial organization on the cascade kinetics was further investigated thanks to the crystalline hierarchical pore structure of the MOF host. These findings pave the way for the design of advanced biocatalytic systems with improved efficiency and durability, potentially transforming applications in sustainable chemical manufacturing and energy conversion.