葡萄糖氧化酶
组合化学
化学
级联
固定化酶
选择性
级联反应
酶
咪唑酯
催化作用
生物催化
材料科学
纳米技术
有机化学
色谱法
反应机理
作者
Jing Wang,Wen Liu,Shanfeng Chen,Xiaoqing Zong,Pengfei Yuan,Xinjie Chen,Xiaodi Li,Yuchao Li,Wei Xue,Jian Dai
标识
DOI:10.1002/adhm.202203035
摘要
Abstract Biocatalytic systems based on enzyme cascade reactions have attracted growing interest in the field of biocatalytic medicine. However, it is a major challenge to reasonably construct enzyme cascade reactions with high stability, selectivity, and catalytic efficiency for the in vivo biocatalytic application. Herein, two‐in‐one engineered glucose oxidase (GOx‐Fe 0 ) is fabricated by a biomineralization strategy, through which a nanozyme (Fe 0 NP) is anchored within the inner cavity of GOx. Then, GOx‐Fe 0 is immobilized in a pH‐sensitive metal–organic framework (MOF) zeolitic imidazolate framework‐8 (ZIF‐8) to establish a stable and effective MOF‐immobilized two‐in‐one engineered enzyme, GOx‐Fe 0 @ZIF‐8. In vitro studies show that GOx‐Fe 0 @ZIF‐8 exhibits excellent stability and high pH/glucose selectivity, and the shorter spacing between cascade enzymes can increase the cascade throughput and effectively improve the reaction efficiency of the enzyme cascade. In vivo experiments exhibit that GOx‐Fe 0 @ZIF‐8 solves the instability and systemic toxicity of free enzymes, and achieves deep tumor penetration and significant chemodynamic therapeutic efficacy through a pH/glucose‐selective enzyme cascade reaction in tumor site. Taken together, such an orchestrated enzyme engineering strategy can effectively improve enzyme stability, selectivity, and enzyme cascade reaction efficiency via chemical transformations, and also provide a promising strategy for the application of biocatalytic cascade reactions in vivo.
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