Fine-Tuning the Micro-Environment to Optimize the Catalytic Activity of Enzymes Immobilized in Multivariate Metal-Organic Frameworks
Fine-Tuning the Micro-Environment to Optimize the Catalytic Activity of Enzymes Immobilized in Multivariate Metal-Organic Frameworks
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DOI：
10.1021/jacs.1c07107
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发表时间：
2021-09-03
影响因子：
15
通讯作者：
Cheng, Lin
中科院分区：
文献类型：
--
作者：
Li, Yi-Ming;Yuan, Jian;Cheng, Lin
酶的结构构象的人工工程化以增强其活性是高度期望和具有挑战性的。在多元金属有机框架（MTV-M0 F）的情况下最好地说明的各向异性网状化学提供了一个平台，以通过框架上的功能变化来修饰M0 F的孔和内表面，以优化内部环境并增强特定目标性质。在这项研究中，我们用MTV方法改变了沸石咪唑酯框架（ZIF）（MOFs的一个子类）中连接体的功能和比例，以证明一种策略，该策略允许我们通过孔微环境中的亲水性变化连续调节框架-酶相互作用来优化包封酶的活性。为了系统地研究这种相互作用，我们开发了组分调整三元图（CAT）方法以接近包封的酶BCL的最佳活性，并揭示了BCL活性与MTV-ZIF-8中的亲水性接头比率之间的非线性相关性，首先递增，然后递减。这些发现表明，沿着横跨ZIF-8晶体的三维空间存在沿着的官能团的空间排列，其具有可以在闭盖和开盖构象之间改变酶结构的独特序列。这些构象的变化，证实了FTIR光谱和荧光研究。优化的BCL@ZIF-8不仅在热和化学上比溶液中的游离BCL更稳定，而且在动力学拆分反应中的催化反应性加倍，产物的ee为99%。
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.