Production of a Novel Protopanaxatriol-Type Ginsenoside by Yeast Cell Factories

被引:4
作者
Zhou, Chen [1 ]
Gong, Ting [1 ]
Chen, Jingjing [1 ]
Chen, Tianjiao [1 ]
Yang, Jinling [1 ]
Zhu, Ping [1 ]
机构
[1] Chinese Acad Med Sci, Peking Union Med Coll, State Key Lab Bioact Subst & Funct Nat Med, Inst Mat Med,NHC Key Lab Biosynth Nat Prod,CAMS Ke, Beijing 100050, Peoples R China
来源
BIOENGINEERING-BASEL | 2023年 / 10卷 / 04期
基金
北京市自然科学基金;
关键词
protopanaxatriol-type ginsenoside; glycosylation; yeast cell factory; metabolic engineering; synthetic biology;
D O I
10.3390/bioengineering10040463
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Ginsenosides, the main active compounds in Panax species, are glycosides of protopanaxadiol (PPD) or protopanaxatriol (PPT). PPT-type ginsenosides have unique pharmacological activities on the central nervous system and cardiovascular system. As an unnatural ginsenoside, 3,12-Di-O-beta-D-glucopyranosyl-dammar-24-ene-3 beta,6 alpha,12 beta,20S-tetraol (3 beta,12 beta-Di-O-Glc-PPT) can be synthesized through enzymatic reactions but is limited by the expensive substrates and low catalytic efficiency. In the present study, we successfully produced 3 beta,12 beta-Di-O-Glc-PPT in Saccharomyces cerevisiae with a titer of 7.0 mg/L by expressing protopanaxatriol synthase (PPTS) from Panax ginseng and UGT109A1 from Bacillus subtilis in PPD-producing yeast. Then, we modified this engineered strain by replacing UGT109A1 with its mutant UGT109A1-K73A, overexpressing the cytochrome P450 reductase ATR2 from Arabidopsis thaliana and the key enzymes of UDP-glucose biosynthesis to increase the production of 3 beta,12 beta-Di-O-Glc-PPT, although these strategies did not show any positive effect on the yield of 3 beta,12 beta-Di-O-Glc-PPT. However, the unnatural ginsenoside 3 beta,12 beta-Di-O-Glc-PPT was produced in this study by constructing its biosynthetic pathway in yeast. To the best of our knowledge, this is the first report of producing 3 beta,12 beta-Di-O-Glc-PPT through yeast cell factories. Our work provides a viable route for the production of 3 beta,12 beta-Di-O-Glc-PPT, which lays a foundation for drug research and development.
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页数:10
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