The nanoconfinement of enzymes within porous scaffolds is a pivotal strategy for constructing robust and industrially relevant biocatalysts. However, a molecular-level understanding of the host-guest interactions that dictate catalytic efficiency remains a significant challenge, largely due to the inherent heterogeneity of enzyme guests and the scarcity of synthetic material hosts that permit atomic-level investigation of their pores upon enzyme loading. Here, we report the design of two redox-active biocatalysts via the encapsulation of cytochrome c within the mesopores of isostructural metal-organic framework (MOF) nanosheets and unveil for the first time adaptive pore deformation in MOF nanosheets governing biocatalytic efficiency. Using low-dose electron microscopy, we directly visualize how the nominally "rigid" MOF pores adaptively remodel─expanding or contracting─to accommodate "flexible" enzymes, a process governed by the interplay between pore surface chemistry and biomolecular flexibility. Crucially, pore expansion facilitates a transition in the heme iron configuration of cytochrome c from a six-coordinated (S = 1/2) to a highly active five-coordinated geometry (S = 3/2). This structural rearrangement enhances catalytic oxidation activity by up to an order of magnitude compared with the free enzyme. The synthetic MOF nanosheet biocatalyst exhibits exceptional efficiency in the degradation of toxic organic pollutants via a high-valent iron(IV)-oxo mechanism, surpassing existing nanocatalysts. These findings challenge the conventional view of solid supports as static carriers and provide new insights into enzymatic reactions under pore confinement.
Yang et al. (Sun,) studied this question.