Recent advances in biotransformation of ginsenosides

doi:10.16085/j.issn.1000-6613.2020-2008

Abstract

Abstract:

Rare ginsenosides are the most important active constituents of ginseng. However, they either contribute to an extremely low proportion of total ginsenosides or do not exist until being transformed in human intestines. Thus, this review summarizes the structure-function relationship and transformation strategies of ginsenosides, focusing on the latest progress of microbial and enzymatic transformation strategies, including transformation of ginsenosides using probiotic and edible-medicinal fungi for the production of functional food, as well as the selection and combination of glycosidases for improving transformation efficiency and productivity of total ginsenosides. It also discusses in depth the effects of genetic engineering, solvent engineering and enzyme immobilization on the transformation efficiency and productivity, and analyzes the potential application value of protein engineering and synthetic biology in improving the catalytic activities and paving the way for large-scale production of rare ginsenosides.

Key words: ginsenoside, biotransformation, microbial transformation, enzymatic transformation, ionic liquid

摘要：

稀有人参皂苷是人参的重要活性成分，但其含量极低或需经过肠道转化才能产生，工业生产中常通过去糖基、脱水等方法将常见人参皂苷转化为稀有人参皂苷。基于此，本文概述了人参皂苷的构效关系及常用转化方法，总结了微生物、酶法定向转化人参皂苷的最新进展，着重介绍了益生菌、食药用真菌转化人参皂苷制备功能食品，以及糖苷酶筛选和组合在提高人参总皂苷转化效率及产率等方面的研究进展；同时探讨了基因工程、溶剂工程、固定化酶等技术对人参皂苷转化效率、产率的影响，展望了蛋白质工程、合成生物学等方法在人参皂苷转化及合成方面的潜在应用价值，为稀有人参皂苷的规模化生产提供了基础。

关键词: 人参皂苷, 生物转化, 微生物催化, 酶催化, 离子液体

CLC Number:

TQ469

ZHAO Jing, WANG Pan, LIU Yannan, FU Rongzhan, DUAN Zhiguang, FAN Daidi. Recent advances in biotransformation of ginsenosides[J]. Chemical Industry and Engineering Progress, 2021, 40(3): 1238-1247.

赵婧, 王盼, 刘彦楠, 傅荣湛, 段志广, 范代娣. 人参皂苷的定向生物转化研究进展[J]. 化工进展, 2021, 40(3): 1238-1247.

Figures/Tables 3

底物	产物	转化菌株	特点	文献
红参提取物	Rd	Lactobacillus plantarum KCCM 11613P	益生菌转化人参皂苷	[27]
Rb1	CK	Lactobacillus paralimentarius LH4	益生菌转化人参皂苷	[28]
Rb1	Rg3、Rh2	Lactobacillus paracasei subsp. tolerans MJM60396	益生菌转化人参皂苷	[29]
Rb1	Rd	Lactobacillus rhamnosus GG	益生菌转化人参皂苷;MRS培养基中添加20g/L纤维二糖提高益生菌β-葡萄糖苷酶产量	[30]
Rb2、Rc	Rd	Bifidobacterium longum RD47	益生菌转化人参皂苷;MRS培养基中添加20g/L抗坏血酸提高α-L-阿拉伯呋喃糖苷酶和α-L-阿拉伯吡喃糖苷酶活性	[31]
Rb1	Rg3、CK	Lactococcus lactis（recombinant）	基因改造益生菌，通过单一菌株发酵及两种菌株顺序发酵分别实现了Rb1向Rg3和CK的转化	[32]
Rb1	Rg3、CK	Cordyceps sinensis, Ascomycota sp	药用虫草真菌转化人参皂苷	[33]
Rb1	Rd	Paecilomyces hepiali	药用虫草真菌蝙蝠蛾拟青霉转化人参皂苷，同时人参促进虫草功效成分腺苷、虫草素和甘露醇的合成，实现协同增效	[34]
Rb1、Rb3	CK、C-Mx、 C-Mc	Fusarium sacchari	土壤真菌转化人参茎叶皂苷	[35]
Rb1、Rb2、Rc、Rd	CK	Aspergillus niger	GRAS认证真菌转化人参皂苷	[36]
Re	Rg1、Rg2、Rh1	Aspergillus niger	GRAS认证真菌转化人参皂苷	[37]
Re	Rh1	Aspergillus oryzae	GRAS认证真菌转化人参皂苷	[38]
红参提取物	Rd、F2、CK	Saccharomyces cerevisiae HJ-014	米酒酿酒酵母转化红参乙醇提取物总皂苷	[39]
Rc	Rd	Cellulosimicrobium aquatile Lyp51	酒曲微生物转化人参皂苷	[40]
Rb1	CK	Paecilomyces bainier sp. 229	人参土壤真菌转化人参皂苷，通过菌种诱变和发酵工艺优化，提高了转化效率，将发酵体积扩大至6L	[41-42]
Rb1	Rg3、CK	GE17-7，GE17-18	人参内生细菌及真菌转化人参皂苷	[43-44]

底物	产物	转化酶及其来源微生物	特点	文献
人参提取物	CK	Sulfolobus solfataricus β-糖苷酶	能够同时转化多种常见人参皂苷	[45]
Rb1、Rb2、Rc、Rd	CK、CY、C-Mc	Sulfolobus acidocaldarius β-糖苷酶	能够同时转化多种常见人参皂苷	[46]
Rb1、Rb2、Rc	CK	Caldicellulosiruptor bescii β-糖苷酶	能够同时转化多种常见人参皂苷，转化率可达100%，产率可达600μmol/(L·h)	[48]
Rb1、Rb2、Rc	CK、CY、C-Mc	Armillaria mellea β-糖苷酶	能够同时转化多种常见人参皂苷，蜜环菌作为功能食品有望与人参皂苷实现协同增效	[49-51]
Rb1、Rb2、Re	CK	Sulfolobus solfataricus β-糖苷酶 Thermotoga petrophila α-L-阿拉伯呋喃糖苷酶	人参提取物、红参提取物及人参叶提取物向CK的转化率可达100%，产率分别可达276mg/(L·h)、196mg/(L·h)及420mg/(L·h)	[52]
Rb1、Rb2、Rc、Rd	20(S)-Rg3	Thermotoga petrophlia β-葡萄糖苷酶 Thermotoga thermarum DSM5069 $α$ -1,6-L-阿拉伯呋喃糖苷酶 Thermotoga petrophlia β-葡萄糖苷酶	能够在3h内、90℃、pH 5.0条件下将10g/L PPD型总皂苷转化为3.93g/L 20(S)-Rg3,转化率可达98.19%，产率可达1.31g/(L·h)	[53]

底物	产物	转化酶及其来源微生物	特点	文献
人参提取物	CK	Sulfolobus solfataricus β-糖苷酶	能够同时转化多种常见人参皂苷	[45]
Rb1、Rb2、Rc、Rd	CK、CY、C-Mc	Sulfolobus acidocaldarius β-糖苷酶	能够同时转化多种常见人参皂苷	[46]
Rb1、Rb2、Rc	CK	Caldicellulosiruptor bescii β-糖苷酶	能够同时转化多种常见人参皂苷，转化率可达100%，产率可达600μmol/(L·h)	[48]
Rb1、Rb2、Rc	CK、CY、C-Mc	Armillaria mellea β-糖苷酶	能够同时转化多种常见人参皂苷，蜜环菌作为功能食品有望与人参皂苷实现协同增效	[49-51]
Rb1、Rb2、Re	CK	Sulfolobus solfataricus β-糖苷酶 Thermotoga petrophila α-L-阿拉伯呋喃糖苷酶	人参提取物、红参提取物及人参叶提取物向CK的转化率可达100%，产率分别可达276mg/(L·h)、196mg/(L·h)及420mg/(L·h)	[52]
Rb1、Rb2、Rc、Rd	20(S)-Rg3	Thermotoga petrophlia β-葡萄糖苷酶 Thermotoga thermarum DSM5069 $α$ -1,6-L-阿拉伯呋喃糖苷酶 Thermotoga petrophlia β-葡萄糖苷酶	能够在3h内、90℃、pH 5.0条件下将10g/L PPD型总皂苷转化为3.93g/L 20(S)-Rg3,转化率可达98.19%，产率可达1.31g/(L·h)	[53]

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