School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, P. R. China.
Avogadral Solutions, 3130 Grants Lake Boulevard #18641, Sugar Land, Texas 77496, United States.
J Am Chem Soc. 2021 Sep 22;143(37):15378-15390. doi: 10.1021/jacs.1c07107. Epub 2021 Sep 3.
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% of the products.
人工工程学中，酶的结构构象的改变以提高其活性是非常理想和具有挑战性的。各向异性的网状化学，在多变量金属有机骨架（MTV-MOFs）的情况下得到了最好的说明，为修饰 MOF 的孔和内表面提供了一个平台，使框架的功能变化具有多样性，从而优化内部环境并增强特定目标的性能。在这项研究中，我们改变了沸石咪唑骨架（ZIFs）的配体的功能和比例，用 MTV 方法来演示一种策略，通过在孔的微环境中改变亲水性，连续调整框架-酶相互作用，从而优化包裹酶的活性。为了系统地研究这种相互作用，我们开发了成分调整三元图（CAT）方法来接近包裹酶 BCL 的最佳活性，并揭示了 BCL 活性与 MTV-ZIF-8 中亲水性配体比例之间的非线性相关性，首先是递增，然后是递减。这些发现表明，在 ZIF-8 晶体的三维空间中，沿着三个方向排列着功能基团，具有独特的序列，可以在闭盖和开盖构象之间改变酶的结构。这些构象变化通过傅里叶变换红外光谱和荧光研究得到了证实。优化后的 BCL@ZIF-8 不仅在溶液中的自由 BCL 更热和化学稳定，而且在动力学拆分反应中的催化反应性提高了一倍，产物的转化率达到了 99%。
