长糖链皂苷的生物合成研究进展

doi:10.12211/2096-8280.2025-049

摘要/Abstract

摘要：

含有多个糖基的长糖链皂苷是常见的植物次生代谢产物，具有调节免疫、抗肿瘤、降脂等药理活性，糖链组成差异是其结构多样性的重要原因。近期，英国约翰英纳斯中心Anne Osbourn教授团队和美国佐治亚大学Jim Leebens-Mack教授团队在Nat. Chem. Biol.期刊上发表了一篇文章，解析了肥皂草中八糖皂苷Saponarioside B的生物合成途径。其他长糖链皂苷如avenacin A-1、yossoside V、α-tomatine、QS-21等的生物合成途径也已于近年阐明。本文将结合相关研究，针对长糖链皂苷生物合成途径中的糖基化酶进行评论，为长糖链皂苷的生物合成酶挖掘与生物制造提供思路，为植物源皂苷的合成生物学提供线索。

关键词: 长糖链皂苷, 生物合成, 糖基化反应, 糖基转移酶

Abstract:

Saponins, featuring multiple glycosyl moieties in long sugar-chains, are significant plant secondary metabolites known for their diverse pharmacological properties, including immunomodulation, antitumor activity, and lipid-lowering effects. Variations in sugar chain composition critically contribute to their structural diversity. Recently, the biosynthetic pathway of Saponarioside B, an octasaccharide saponin derived from Saponaria officinalis, was elucidated through collaborative research efforts led by Prof. Anne Osbourn (John Innes Centre, UK) and Prof. Jim Leebens-Mack (University of Georgia, USA), as published in Nature Chemical Biology. The biosynthetic pathways of other long sugar-chain saponins, such as avenacin A-1, yossoside V, α-tomatine, and QS-21, have also been elucidated in recent years. This review aims to explore the glycosylation reactions and their catalytic enzymes in the biosynthesis of long sugar-chain saponins, integrating recent advances to update enzyme discoveries, optimize biomanufacturing strategies, and develop synthetic biology approaches for plant-derived saponins.

Key words: long sugar-chain saponins, biosynthesis, glycosylation reaction, glycosyltransferase

中图分类号:

Q816

肖和, 姚明菊, 乔雪. 长糖链皂苷的生物合成研究进展[J]. 合成生物学, DOI: 10.12211/2096-8280.2025-049.

XIAO He, YAO Mingju, QIAO Xue. Advances in the biosynthesis of long sugar-chain saponins[J]. Synthetic Biology Journal, DOI: 10.12211/2096-8280.2025-049.

图/表 4

图1 知名长糖链皂苷的结构式［5］［6］［7］［8］

Fig. 1 Chemical structures of known long sugar-chain saponins[5][6][7][8]

图2 Saponarioside B的糖链生物合成途径

Fig. 2 The biosynthetic pathway to Saponarioside B

图3 皂苷生物合成的UDP糖供体及部分糖供体的合成过程（a，糖基转移酶研究较多的UDP-糖供体；b，UDP-芹糖的生物合成途径；c，UDP-岩藻糖及UDP-喹诺糖的结构式；d，QS-21合成过程中的岩藻糖基化反应及UDP-岩藻糖生物合成途径。A，苷元；UAXS，UDP-芹糖/木糖合酶；UGD，UDP-葡萄糖-4，6-脱氢酶；4KD， 4-酮基还原酶；SDR，短链脱氢酶/还原酶）

Fig. 3 Sugar donors of saponins(a. UDP-sugar donors for extensively studied glycosyltransferases; b. The biosynthetic pathway for UDP- apiose; c. Structures of UDP-fucose and UDP-quinovose; d. The fucosylation reaction in the biosynthesis of QS-21 and the biosynthetic pathway of UDP-fucose. A, aglycone; UAXS, UDP-apiose/UDP-xylose synthase; UGD, UDP-D-glucose 4,6-dehydratase; 4KD, 4-keto-reductase; SDR, short-chain dehydrogenase/reductase.)

图4 糖苷类化合物糖基转移酶的序列相似度分析(UGT74H5, XRL31186.1; UGT74H6, ACD03261.1; UGT74H7, ACD03246.1; UGT91G16, QHG10987.1; UGT71C3, CAE7210926.1; UGT73B2, OAO97622.1; UGT73B3, OAO99384.1; UGT73B5, OAP10701.1; UGT73C6, OAP07438.1; UGT74B1, OAP18511.1; UGT74D1, OAP11252.1; UGT74E2, OAP17332.1; UGT74F2, OAP07463.1; UGT75B1, OAP16927.1; UGT75C1, Q0WW21.2; UGT76D1, OAP10891.1; UGT76E1, OAO90200.1; UGT76E12, OAP06710.1; UGT78D2, OAO89857.1; UGT79B6, NP_200212.1; UGT84A1, OAO99238.1; UGT84A2, OAP06181.1; UGT84A3, OAP00592.1; UGT84A4, OAO98847.1; UGT84B1, OAP11221.1; UGT88A1, OAP04631.1; UGT89B1, OAP14423.1; UGT84A9a, CAS03354.1; CaUGT3, BAH80312.1; UGT707B1, CCG85331.1; CsGT45, ACM66950.1; DgUGT1, BAO66179.1; DicGT1, BAD52003.1; FaGT2, Q66PF4.1; FaGT6, Q2V6K0.1; FaGT7, Q2V6J9.1; UGT71K3, P0DO49.1; UGT73B23, XP_004304022.1; Fh3GT1, ADK75021.1; GgSGT, BAG14302.1; GhHGT8, Q9ZR25.1; GjUGT75L6, F8WKW0.1; GmIF7GT, NP_001235161.1; UGT79B30, BAR88077.1; Gt5GT7, B2NID7.1; GtFla3OGT, Q96493.1; UGT74M1, ABK76266.1; HvUGT13248, ADC92550.1; Ihant5GT, BAD06874.1; In3GGT, Q53UH4.1; LbUGT73A10, BAG80536.1; UGT75L17, AAX16493.1; UGT75L4, ABL85474.1; NtSAGTase, AAF61647.1; NtToGT1, Q9AT54.1; NtToGT2, AAB36652.1; UGT707A3, BAC83989.1; UGT709A4, BAC80066.1; PcF7GT, AAY27090.1; Pf3R4, BAA36421.1; UGT88A7, BAG31949.1; UGTPg45, AKA44586.1; UGT90A7, ACB56926.1; UGT84A23, ANN02875.1; UGT84A24, ANN02877.1; QsUGT74BX1, WEU75090.1; QsUGT73CY2, WEU75102.1; QsUGT73CY3, WEU75103.1; QsUGT73CX1, WEU75094.1; QsUGT73CX2, WEU75095.1; QsUGT73CU3, WEU75099.1; QsUGT91AR1, WEU75091.1; QsUGT91AQ1, WEU75104.1; RhGT1, BAD99560.1; SoUGT74CD1, WWM48152.1; SoUGT73M2, WWM48153.1; SoUGT73CC6, WWM48156.1; SoUGT73DL1, WWM48158.1; SoUGT79T1, WWM48161.1; SoUGT79L3, WWM48150.1; ScbUBGT, BAA83484.1; ScUGT5, BAJ11653.1; UGT74AC1, AEM42999.1; SlGtsatom, CAI62049.1; UGT74G1, Q6VAA6.1; Via5GT, AHL68667.1; VlResOGT, ABH03018.1; UGT94F1, BAI44133.1; VvGT1, AAB81683.1; ZmIAGT, AAA59054.1)

Fig. 4 Sequence similarity analysis of glycosyltransferases involved in glycoside biosynthesis

参考文献 12

[1]	CHOI S H, J-B AHN, KOZUKUE N, et al. Structure–activity relationships of α-, β1-, γ-, and δ-tomatine and tomatidine against human breast (MDA-MB-231), gastric (KATO-III), and prostate (PC3) cancer cells [J]. Journal of Agricultural and Food Chemistry, 2012, 60(15): 3891-9.
[2]	ODA K, MATSUDA H, MURAKAMI T, et al. Relationship between adjuvant activity and amphipathic structure of soyasaponins [J]. Vaccine, 2003, 21(17-18): 2145-51.
[3]	JO S, EL-DEMERDASH A, OWEN C, et al. Unlocking saponin biosynthesis in soapwort [J]. Nature Chemical Biology, 2025, 21: 215-26.
[4]	CUI X, MA X, LI C, et al. A review: structure-activity relationship between saponins and cellular immunity [J]. Molecular Biology Reports, 2023, 50: 2779-93.
[5]	JOZWIAK A, SONAWANE P D, PANDA S, et al. Plant terpenoid metabolism co-opts a component of the cell wall biosynthesis machinery [J]. Nature Chemical Biology, 2020, 16: 740-8.
[6]	REED J, ORME A, EL-DEMERDASH A, et al. Elucidation of the pathway for biosynthesis of saponin adjuvants from the soapbark tree [J]. Science, 2023, 379: 1252-64.
[7]	LI Y, LEVEAU A, ZHAO Q, et al. Subtelomeric assembly of a multi-gene pathway for antimicrobial defense compounds in cereals [J]. Nature Communications, 2021, 12(2563): 1-13.
[8]	AL. M I E. Biosynthesis of antinutritional alkaloids in solanaceous crops is mediated by clustered genes [J]. Science, 2013, 341: 175-9.
[9]	CHUNG S Y, SEKI H., FUJISAWA Y.ET AL. A cellulose synthase-derived enzyme catalyses 3-O-glucuronosylation in saponin biosynthesis [J]. Nature Communications, 2020, 11(5664): 1-11.
[10]	LIU Y, ZHAO X, GAN F, et al. Complete biosynthesis of QS-21 in engineered yeast [J]. Nature, 2024, 629: 937-44.
[11]	Qu G, Song Y, Xu X, et al. De novo biosynthesis of mogroside V by multiplexed engineered yeasts. Metabolic Engineering, 2025, 88: 160-171.
[12]	ORME A, LOUVEAU T, STEPHENSON M J, et al. A scaffold protein manages the biosynthesis of steroidal defense metabolites in plants [J]. Science, 2025, 386: 1366-72.

[1]	盛周煌, 陈智仙, 张彦. 酵母甘露糖蛋白的研究进展[J]. 合成生物学, 2025, 6(2): 408-421.
[2]	鲁锦畅, 武耀康, 吕雪芹, 刘龙, 陈坚, 刘延峰. 神经酰胺类鞘脂的绿色生物制造[J]. 合成生物学, 2025, 6(2): 422-444.
[3]	韦灵珍, 王佳, 孙新晓, 袁其朋, 申晓林. 黄酮类化合物生物合成及其在化妆品中应用的研究[J]. 合成生物学, 2025, 6(2): 373-390.
[4]	肖森, 胡立涛, 石智诚, 王发银, 余思婷, 堵国成, 陈坚, 康振. 可控分子量透明质酸的生物合成研究进展[J]. 合成生物学, 2025, 6(2): 445-460.
[5]	汤传根, 王璟, 张烁, 张昊宁, 康振. 功能肽合成和挖掘策略研究进展[J]. 合成生物学, 2025, 6(2): 461-478.
[6]	黄姝涵, 马赫, 罗云孜. 生物合成红景天苷的研究进展[J]. 合成生物学, 2025, 6(2): 391-407.
[7]	仲泉周, 单依怡, 裴清云, 金艳芸, 王艺涵, 孟璐远, 王歆韵, 张雨鑫, 刘坤媛, 王慧中, 冯尚国. 生物合成法生产α-熊果苷的研究进展[J]. 合成生物学, 2025, 6(1): 118-135.
[8]	竺方欢, 岑雪聪, 陈振. 微生物合成二元醇研究进展[J]. 合成生物学, 2024, 5(6): 1367-1385.
[9]	刘益宁, 蒲伟, 杨金星, 王钰. ω-氨基酸与内酰胺的生物合成研究进展[J]. 合成生物学, 2024, 5(6): 1350-1366.
[10]	李庚, 申晓林, 孙新晓, 王佳, 袁其朋. 过氧化物酶的重组表达和应用研究进展[J]. 合成生物学, 2024, 5(6): 1498-1517.
[11]	郑皓天, 李朝风, 刘良叙, 王嘉伟, 李恒润, 倪俊. 负碳人工光合群落的设计、优化与应用[J]. 合成生物学, 2024, 5(5): 1189-1210.
[12]	程晓雷, 刘天罡, 陶慧. 萜类化合物的非常规生物合成研究进展[J]. 合成生物学, 2024, 5(5): 1050-1071.
[13]	刘子健, 穆柏杨, 段志强, 王璇, 陆晓杰. 与核酸兼容的化学反应开发进展[J]. 合成生物学, 2024, 5(5): 1102-1124.
[14]	张守祺, 王涛, 孔尧, 邹家胜, 刘元宁, 徐正仁. 天然产物的化学-酶法合成：方法与策略的演进[J]. 合成生物学, 2024, 5(5): 913-940.
[15]	谢向前, 郭雯, 王欢, 李进. 含氨基乙烯半胱氨酸核糖体肽的生物合成与化学合成[J]. 合成生物学, 2024, 5(5): 981-996.