Institute of Structural Pharmacology & TCM Chemical Biology, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
J Nat Prod. 2024 Apr 26;87(4):1246-1267. doi: 10.1021/acs.jnatprod.3c00630. Epub 2024 Mar 6.
Ginsenosides, the primary pharmacologically active constituents of the genus, have demonstrated a variety of medicinal properties, including anticardiovascular disease, cytotoxic, antiaging, and antidiabetes effects. However, the low concentration of ginsenosides in plants and the challenges associated with their extraction impede the advancement and application of ginsenosides. Heterologous biosynthesis represents a promising strategy for the targeted production of these natural active compounds. As representative triterpenoids, the biosynthetic pathway of the aglycone skeletons of ginsenosides has been successfully decoded. While the sugar moiety is vital for the structural diversity and pharmacological activity of ginsenosides, the mining of uridine diphosphate-dependent glycosyltransferases (UGTs) involved in ginsenoside biosynthesis has attracted a lot of attention and made great progress in recent years. In this paper, we summarize the identification and functional study of UGTs responsible for ginsenoside synthesis in both plants, such as and , and microorganisms including and . The UGT-related microbial cell factories for large-scale ginsenoside production are also mentioned. Additionally, we delve into strategies for UGT mining, particularly potential rapid screening or identification methods, providing insights and prospects. This review provides insights into the study of other unknown glycosyltransferases as candidate genetic elements for the heterologous biosynthesis of rare ginsenosides.
人参属植物中的主要药效成分——人参皂苷具有多种药用特性,包括抗心血管疾病、细胞毒性、抗老化和抗糖尿病作用。然而,植物中人参皂苷的浓度较低,以及其提取所面临的挑战,阻碍了人参皂苷的发展和应用。异源生物合成代表了靶向生产这些天然活性化合物的有前途的策略。作为代表性的三萜类化合物,人参皂苷苷元骨架的生物合成途径已被成功解码。虽然糖基部分对于人参皂苷的结构多样性和药理活性至关重要,但参与人参皂苷生物合成的尿苷二磷酸依赖性糖基转移酶(UGTs)的挖掘近年来引起了广泛关注并取得了重大进展。在本文中,我们总结了植物(如 和 )和微生物(如 和 )中负责人参皂苷合成的 UGT 的鉴定和功能研究。还提到了用于大规模人参皂苷生产的 UGT 相关微生物细胞工厂。此外,我们深入探讨了 UGT 挖掘的策略,特别是潜在的快速筛选或鉴定方法,提供了见解和展望。本综述为人参属中其他未知糖基转移酶作为稀有人参皂苷异源生物合成的候选遗传元件的研究提供了思路。