Fine-Tuning the Micro-Environment to Optimize the Catalytic Activity of Enzymes Immobilized in Multivariate Metal–Organic Frameworks

Abstract

The artificial engineering of an enzyme's structural conformation to enhance its activity is highly desired and challenging. Anisotropic reticular chemistry, best illustrated in the case of multivariate metal−organic frameworks (MTV-MOFs), provides a platform to modify a MOF's pore and inner-surface with functionality variations on frameworks to optimize the interior environment and to enhance the specifically targeted property. In this study, we altered the functionality and ratio of linkers in zeolitic imidazolate frameworks (ZIFs), a subclass of MOFs, with the MTV approach to demonstrate a strategy that allows us to optimize the activity of the encapsulated enzyme by continuously tuning the framework−enzyme interaction through the hydrophilicity change in the pores' microenvironment. To systematically study this interaction, we developed the component-adjustment-ternary plot (CAT) method to approach the optimal activity of the encapsulated enzyme BCL and revealed a nonlinear correlation, first incremental and then decremental, between the BCL activity and the hydrophilic linker' ratios in MTV-ZIF-8. These findings indicated there is a spatial arrangement of functional groups along the three-dimensional space across the ZIF-8 crystal with a unique sequence that could change the enzyme structure between closed-lid and open-lid conformations. These conformation changes were confirmed by FTIR spectra and fluorescence studies. The optimized BCL@ZIF-8 is not only thermally and chemically more stable than free BCL in solution, but also doubles the catalytic reactivity in the kinetic resolution reaction with 99% ee of the products.

Metal–organic framework (MOF)-, covalent-organic framework (COF)-, and porous-organic polymers (POP)-catalyzed selective C–H bond activation and functionalization reactions

“…State-of-the-art MOFs are complex/multicomponent/multivariate MOFs prepared through various strategies, 131,320,332,334,336,337,351–360 possessing multiple active sites, which target synergistic/cooperative photocatalysis and catalysis and advanced tandem reactions.…”

“…338 Photocatalyst-based MOF systems possess plentiful reactive sites and increased electron-hole pair lifetime (decrease in photogenerated charge recombination rate) and charge mobility compared to the traditional semiconductors. 340 State-of-the-art MOFs are complex/multicomponent/multivariate MOFs prepared through various strategies, 131,320,332,334,336,337,[351][352][353][354][355][356][357][358][359][360] possessing multiple active sites, which target synergistic/cooperative photocatalysis and catalysis and advanced tandem reactions.…”

Enzyme Immobilization and Co-Immobilization: Main Framework, Advances and Some Applications

“…Thus, the hydrogen bonds of the framework could be adequately adjusted to be strong enough to interact with enzyme surface and generate an optimized conformation, albeit leaving untouched the structure of the buried catalytic triad. Ultimately, this allowed maintaining 99% enantiomeric excess of the products in several kinetic resolution reactions that were evaluated [136]. Within the same scope, Ruiz and co-workers, showed that depending on the type of carrier, and concomitantly immobilization method used and corresponding enzyme-enzyme and enzyme-surface interactions, the catalytic features of a psychrophilic lipase were modified.…”

Green and Scalable Fabrication of High‐Performance Biocatalysts Using Covalent Organic Frameworks as Enzyme Carriers

“…Considerable efforts have been devoted to constructing efficient enzyme‐immobilization systems through strategies such as adsorption, covalent bonding, crosslinking, using various materials (e.g., polymer, silica, metal oxide) as the matrix [10–18] . However, vast limitations still remain in this field, such as encapsulation of large‐size enzymes, substrate/product transfer issues caused by nonporous carriers, leaching or conformational change of enzymes during the immobilization process [19–22] . It is also of great challenge to elaborately design the immobilization systems to adapt the characteristics of enzyme/reaction or expediently fabricate the immobilized biocatalysts on a large scale [23] .…”