Li Yangyang, Du Guocheng, Chen Jian, Lv Xueqin, Liu Long
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; Science Center for Future Foods, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China.
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; Science Center for Future Foods, Jiangnan University, Wuxi 214122, China.
Curr Opin Biotechnol. 2025 Jun;93:103315. doi: 10.1016/j.copbio.2025.103315. Epub 2025 May 9.
Human milk oligosaccharides (HMOs) play a pivotal role in infant health through their multifunctional bioactive properties. Recent advances in synthetic biology have revolutionized microbial platforms for HMO biosynthesis, with glycosyltransferases (GTs) emerging as indispensable biocatalytic tools that drive enzymatic lactose glycosylation to generate diversified oligosaccharides. This review systematically analyzes GT structural biology, elucidating conserved domains and catalytic mechanisms through crystallographic studies. We summarize contemporary optimization strategies for enhancing GT functionality, including solubility enhancement, catalytic efficiency improvement, and substrate specificity engineering via structure-guided rational design. Emerging deep learning algorithms demonstrate transformative potential in GT modifications and de novo design, providing innovative solutions to overcome bottlenecks in industrial-scale HMO synthesis. These approaches establish a framework for the precision engineering of carbohydrate-active enzymes.
人乳寡糖（HMOs）凭借其多功能生物活性特性在婴儿健康中发挥着关键作用。合成生物学的最新进展彻底改变了用于HMO生物合成的微生物平台，糖基转移酶（GTs）作为不可或缺的生物催化工具出现，驱动酶促乳糖糖基化以生成多样化的寡糖。本综述系统地分析了GT结构生物学，通过晶体学研究阐明了保守结构域和催化机制。我们总结了当代增强GT功能的优化策略，包括通过结构导向的合理设计提高溶解度、改善催化效率和进行底物特异性工程。新兴的深度学习算法在GT修饰和从头设计中展现出变革潜力，为克服工业规模HMO合成中的瓶颈提供了创新解决方案。这些方法为碳水化合物活性酶的精准工程建立了一个框架。
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