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Characterization an...
Characterization and protein engineering of glycosyltransferases for the biosynthesis of diverse hepatoprotective cycloartane-type saponins in Astragalus membranaceus
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- Chen, Kuan (author)
- Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China.;Capital Med Univ, Beijing Friendship Hosp, Beijing Inst Clin Pharm, Beijing, Peoples R China.
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- Zhang, Meng (author)
- Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China.
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- Gao, Baihan (author)
- Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China.
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- Hasan, Aobulikasimu (author)
- Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China.
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- Li, Junhao (author)
- Uppsala universitet,Kemisk och biomolekylär fysik
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- Bao, Yang'oujie (author)
- Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China.
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- Fan, Jingjing (author)
- Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China.
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- Yu, Rong (author)
- Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China.
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- Yi, Yang (author)
- Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China.
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- Ågren, Hans (author)
- Uppsala universitet,Kemisk och biomolekylär fysik
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- Wang, Zilong (author)
- Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China.
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- Liu, Haiyang (author)
- Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Yunnan, Peoples R China.;Chinese Acad Sci, Kunming Inst Bot, Yunnan Key Lab Nat Med Chem, Kunming, Yunnan, Peoples R China.
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- Ye, Min (author)
- Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China.
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- Qiao, Xue (author)
- Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China.
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Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China;Capital Med Univ, Beijing Friendship Hosp, Beijing Inst Clin Pharm, Beijing, Peoples R China. Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China. (creator_code:org_t)
- 2023-01-05
- 2023
- English.
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In: Plant Biotechnology Journal. - : John Wiley & Sons. - 1467-7644 .- 1467-7652. ; 21:4, s. 698-710
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Abstract
Subject headings
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- Although plant secondary metabolites are important source of new drugs, obtaining these compounds is challenging due to their high structural diversity and low abundance. The roots of Astragalus membranaceus are a popular herbal medicine worldwide. It contains a series of cycloartane-type saponins (astragalosides) as hepatoprotective and antivirus components. However, astragalosides exhibit complex sugar substitution patterns which hindered their purification and bioactivity investigation. In this work, glycosyltransferases (GT) from A. membranaceus were studied to synthesize structurally diverse astragalosides. Three new GTs, AmGT1/5 and AmGT9, were characterized as 3-O-glycosyltransferase and 25-O-glycosyltransferase of cycloastragenol respectively. AmGT1(G146V/I) variants were obtained as specific 3-O-xylosyltransferases by sequence alignment, molecular modelling and site-directed mutagenesis. A combinatorial synthesis system was established using AmGT1/5/9, AmGT1(G146V/S) and the reported AmGT8 and AmGT8(A394F). The system allowed the synthesis of 13 astragalosides in Astragalus root with conversion rates from 22.6% to 98.7%, covering most of the sugar-substitution patterns for astragalosides. In addition, AmGT1 exhibited remarkable sugar donor promiscuity to use 10 different donors, and was used to synthesize three novel astragalosides and ginsenosides. Glycosylation remarkably improved the hepatoprotective and SARS-CoV-2 inhibition activities for triterpenoids. This is one of the first attempts to produce a series of herbal constituents via combinatorial synthesis. The results provided new biocatalytic tools for saponin biosynthesis.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- astragalosides
- biosynthesis
- glycosyltransferases
- protein engineering
- Astragalus membranaceus
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Chen, Kuan
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Zhang, Meng
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Gao, Baihan
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Hasan, Aobulikas ...
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Li, Junhao
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Bao, Yang'oujie
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show more...
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Fan, Jingjing
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Yu, Rong
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Yi, Yang
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Ågren, Hans
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Wang, Zilong
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Liu, Haiyang
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Ye, Min
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Qiao, Xue
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Plant Biotechnol ...
- By the university
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Uppsala University