Diao Hong-Juan, Lin Li-Ming, Xu Li-Yuan, Yao Jia-Hao, Zheng Ren-Chao, Zheng Yu-Guo
Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, PR China; Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology, Hangzhou 310014, PR China.
Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, PR China; Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology, Hangzhou 310014, PR China.
Biotechnol Adv. 2025 Sep;82:108601. doi: 10.1016/j.biotechadv.2025.108601. Epub 2025 May 13.
Catalytic promiscuity in enzymes refers to their ability to catalyze multiple chemically distinct reactions in addition to their native activity. The increasing discovery of additional enzymes exhibiting catalytic promiscuity has underscored the significance of this trait in nature. The catalytic promiscuity of enzymes offers new avenues for functional redesign. Through protein engineering, existing enzymes can be modified to expand their natural catalytic boundaries. Furthermore, de novo designed artificial enzymes can achieve novel enzymatic reactions, broadening the scope of enzyme-catalyzed applications. Given that catalytic promiscuity plays a fundamental role in enzyme evolution, comprehensive research on its origins and influencing factors is essential. In this review, we comprehensively examine the factors influencing catalytic promiscuity, including variations in substrate binding modes in pre-reaction states, the instability of key high-energy intermediates, and the roles of critical residues in catalytic mechanisms. Moreover, altering the enzyme's catalytic environment can also induce novel types of catalytic reactions, such as light-induced promiscuous reactions catalyzed by cofactor-dependent oxidoreductase enzymes. Additionally, we summarize the current protein engineering technologies and strategies aimed at enhancing the activity and stereoselectivity of target enzymes to meet industrial requirements.
酶的催化多效性是指它们除了具有天然活性外，还能够催化多种化学性质不同的反应。越来越多具有催化多效性的酶被发现，这凸显了该特性在自然界中的重要性。酶的催化多效性为功能重新设计提供了新途径。通过蛋白质工程，可以对现有酶进行修饰，以扩大其天然催化边界。此外，从头设计的人工酶可以实现新型酶促反应，拓宽酶催化应用的范围。鉴于催化多效性在酶进化中起着基础性作用，对其起源和影响因素进行全面研究至关重要。在本综述中，我们全面考察了影响催化多效性的因素，包括反应前状态下底物结合模式的变化、关键高能中间体的不稳定性以及催化机制中关键残基的作用。此外，改变酶的催化环境也可以诱导新型催化反应，例如辅因子依赖性氧化还原酶催化的光诱导多效反应。此外，我们总结了当前旨在提高目标酶的活性和立体选择性以满足工业需求的蛋白质工程技术和策略。
