Huang Wen-Qian, Wang Ying-Xia, Tian Wei-Sheng, Wang Juan, Tu Peng-Fei, Wang Xiao-Hui, Shi She-Po, Liu Xiao
Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine Beijing 100029, China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Beijing 100191, China.
Zhongguo Zhong Yao Za Zhi. 2023 Jan;48(2):336-348. doi: 10.19540/j.cnki.cjcmm.20221017.102.
As a biocatalyst, enzyme has the advantages of high catalytic efficiency, strong reaction selectivity, specific target products, mild reaction conditions, and environmental friendliness, and serves as an important tool for the synthesis of complex organic molecules. With the continuous development of gene sequencing technology, molecular biology, genetic manipulation, and other technologies, the diversity of enzymes increases steadily and the reactions that can be catalyzed are also gradually diversified. In the process of enzyme-catalyzed synthesis, the majority of common enzymatic reactions can be achieved by single enzyme catalysis, while many complex reactions often require the participation of two or more enzymes. Therefore, the combination of multiple enzymes together to construct the multi-enzyme cascade reactions has become a research hotspot in the field of biochemistry. Nowadays, the biosynthetic pathways of more natural products with complex structures have been clarified, and secondary metabolic enzymes with novel catalytic activities have been identified, discovered, and combined in enzymatic synthesis of natural/unnatural molecules with diverse structures. This study summarized a series of examples of multi-enzyme-catalyzed cascades and highlighted the application of cascade catalysis methods in the synthesis of carbohydrates, nucleosides, flavonoids, terpenes, alkaloids, and chiral molecules. Furthermore, the existing problems and solutions of multi-enzyme-catalyzed cascade method were discussed, and the future development direction was prospected.
作为一种生物催化剂，酶具有催化效率高、反应选择性强、目标产物专一、反应条件温和以及环境友好等优点，是合成复杂有机分子的重要工具。随着基因测序技术、分子生物学、基因操作等技术的不断发展，酶的多样性稳步增加，可催化的反应也逐渐多样化。在酶催化合成过程中，大多数常见的酶促反应可通过单一酶催化实现，而许多复杂反应往往需要两种或更多种酶的参与。因此，将多种酶组合在一起构建多酶级联反应已成为生物化学领域的研究热点。如今，更多结构复杂的天然产物的生物合成途径已被阐明，具有新型催化活性的次生代谢酶已被鉴定、发现，并应用于结构多样的天然/非天然分子的酶促合成中。本研究总结了一系列多酶催化级联反应的实例，并重点介绍了级联催化方法在碳水化合物、核苷、黄酮类化合物、萜类化合物、生物碱和手性分子合成中的应用。此外，还讨论了多酶催化级联方法存在的问题及解决方案，并对未来的发展方向进行了展望。
