N-糖链合成的研究进展

doi:10.12211/2096-8280.2025-053

摘要/Abstract

摘要：

糖基化是一种常见的蛋白质翻译后修饰，N-糖链的合成起始于内质网并在高尔基体中完成。糖链结构的精确合成与调控不仅促进蛋白质结构与功能的成熟，还与多种疾病的发生发展密切相关。近年来，N-糖链生物合成机制陆续阐明，使其合成通路逐渐清晰，进而推动了合成方法的发展和应用转化。本综述系统梳理了近年来N-糖链合成领域的重要工作和进展，旨在为糖合成生物学研究提供可行的策略。在解析N-糖链体内合成的过程中，活体成像与单细胞分析、多组学整合等前沿技术的涌现，使糖链合成动态网络相关研究取得了突破性进展；在N-糖链体外合成的研究中，酶法催化、化学酶法结合、细胞工厂等技术的发展和优化实现了复杂糖链的可控合成，为其功能研究和应用提供了重要工具；在疾病诊断与干预方面，神经退行性疾病、肿瘤和心血管疾病等多种疾病中存在异常合成的N-糖链，为诊断标志物的发现和干预策略的设计提供了新思路。

关键词: N-糖链生物合成, N-糖链体外合成, 糖生物学, 糖生物标志物, 疾病诊断与干预

Abstract:

Glycosylation is a common post-translational modification of proteins. The biosynthesis of N-glycans initiates in the endoplasmic reticulum through the transfer of a lipid-linked oligosaccharide precursor to nascent polypeptides, followed by extensive remodeling and maturation in the Golgi apparatus. This sophisticated biosynthetic pathway involves the coordinated action of numerous glycosidases and glycosyltransferases that precisely control glycan structure and composition. The accurate synthesis and regulation of N-glycan structures are not only crucial for proper protein folding, stability, and functional maturation but also play pivotal roles in various physiological and pathological processes, including cell-cell communication, immune response, and disease pathogenesis. In recent years, significant progress has been made in elucidating the molecular mechanisms underlying N-glycan biosynthesis. The identification and characterization of key enzymes involved in the processing pathway have greatly enhanced our understanding of this complex biological system. These fundamental discoveries have in turn facilitated the development of innovative synthetic methodologies and their practical applications in biotechnology and medicine.This comprehensive review systematically summarizes major research achievements and recent advancements in the field of N-glycan synthesis. In investigating in vivo N-glycan biosynthesis, the emergence of cutting-edge technologies including high-resolution live-cell imaging, single-cell analysis, and integrated multi-omics approaches has enabled groundbreaking discoveries regarding the spatiotemporal dynamics and regulatory networks of glycan synthesis. For in vitro synthesis, significant improvements in enzymatic catalysis, chemoenzymatic approaches, and engineered cell factory systems have allowed for the controlled production of structurally defined complex glycans, thereby providing essential tools for functional studies and therapeutic applications.From a clinical perspective, accumulating evidence has demonstrated that aberrant N-glycan structures are closely associated with various human diseases, including neurodegenerative disorders, malignant tumors, and cardiovascular pathologies. These disease-specific glycan alterations not only serve as valuable diagnostic biomarkers but also offer novel therapeutic targets for the development of innovative intervention strategies, such as glycan-based vaccines and antibody therapies. By integrating these recent discoveries, this review highlights the remarkable interdisciplinary progress in N-glycan research and discusses its far-reaching implications for biomedical science and clinical applications.

Key words: N-glycan biosynthesis, N-glycan in vitro synthesis, Glycobiology, Glycan biomarkers, Disease diagnosis and intervention

中图分类号:

Q816

丁怡, 苏敏, 高晓冬, 王宁. N-糖链合成的研究进展[J]. 合成生物学, DOI: 10.12211/2096-8280.2025-053.

Ding Yi, Su Min, Gao Xiaodong, Wang Ning. Advances in Research of N-Glycan Synthesis[J]. Synthetic Biology Journal, DOI: 10.12211/2096-8280.2025-053.

图/表 7

图1 N-糖链体内合成研究中的关键技术

Fig. 1 Key technologies in the in vivoN-glycan biosynthesis research

图2 Rft1催化脂肪醇寡糖跨ER膜转运［38］

Fig. 2 Rft1 catalyzes lipid-linked oligosaccharide translocation across the ER membrane[38]

图3 SUGAR-TARGET用于N-糖链高效合成［64］

Fig. 3 SUGAR-TARGET for the efficient synthesis of N-glycans[64]

图4 化学酶法高效组装N-糖链［60］

Fig. 4 Efficient assembly of N-glycans by chemoenzymatic method[60]

图5 细胞工厂合成目的N-糖链［64］

Fig. 5 Synthesis of target N-glycans in cell factories[64]

图6 N-糖链结构与疾病关联及相关应用

Fig. 6 Disease-associated N-Glycan alterations and their potential applications

图7 癫痫患者细胞表面糖链变化［81］

Fig. 7 Changes in cell surface polysaccharides in MOGHE patients[81]

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