Biosynthetic pathway of prescription bergenin from Bergenia purpurascens and Ardisia japonica
Bergenin is a typical carbon glycoside and the primary active ingredient in antitussive drugs widely prescribed for central cough inhibition in China. The bergenin extraction industry relies on the medicinal plant species Bergenia purpurascens and Ardisia japonica as their resources. However, the be...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Plant Science |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fpls.2023.1259347/full |
| _version_ | 1797366577906057216 |
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| author | Xiang-Yu Liu Xiang-Yu Liu Yi-Na Wang Yi-Na Wang Jiang-Shun Du Jiang-Shun Du Bi-Huan Chen Bi-Huan Chen Kun-Yi Liu Lei Feng Lei Feng Gui-Sheng Xiang Gui-Sheng Xiang Shuang-Yan Zhang Shuang-Yan Zhang Ying-Chun Lu Sheng-Chao Yang Sheng-Chao Yang Guang-Hui Zhang Guang-Hui Zhang Bing Hao Bing Hao |
| author_facet | Xiang-Yu Liu Xiang-Yu Liu Yi-Na Wang Yi-Na Wang Jiang-Shun Du Jiang-Shun Du Bi-Huan Chen Bi-Huan Chen Kun-Yi Liu Lei Feng Lei Feng Gui-Sheng Xiang Gui-Sheng Xiang Shuang-Yan Zhang Shuang-Yan Zhang Ying-Chun Lu Sheng-Chao Yang Sheng-Chao Yang Guang-Hui Zhang Guang-Hui Zhang Bing Hao Bing Hao |
| author_sort | Xiang-Yu Liu |
| collection | DOAJ |
| description | Bergenin is a typical carbon glycoside and the primary active ingredient in antitussive drugs widely prescribed for central cough inhibition in China. The bergenin extraction industry relies on the medicinal plant species Bergenia purpurascens and Ardisia japonica as their resources. However, the bergenin biosynthetic pathway in plants remains elusive. In this study, we functionally characterized a shikimate dehydrogenase (SDH), two O-methyltransferases (OMTs), and a C-glycosyltransferase (CGT) involved in bergenin synthesis through bioinformatics analysis, heterologous expression, and enzymatic characterization. We found that BpSDH2 catalyzes the two-step dehydrogenation process of shikimic acid to form gallic acid (GA). BpOMT1 and AjOMT1 facilitate the methylation reaction at the 4-OH position of GA, resulting in the formation of 4-O-methyl gallic acid (4-O-Me-GA). AjCGT1 transfers a glucose moiety to C-2 to generate 2-Glucosyl-4-O-methyl gallic acid (2-Glucosyl-4-O-Me-GA). Bergenin production ultimately occurs in acidic conditions or via dehydration catalyzed by plant dehydratases following a ring-closure reaction. This study for the first time uncovered the biosynthetic pathway of bergenin, paving the way to rational production of bergenin in cell factories via synthetic biology strategies. |
| first_indexed | 2024-03-08T17:05:46Z |
| format | Article |
| id | doaj.art-40507d1d8c3a401eac673af87fc06ca9 |
| institution | Directory Open Access Journal |
| issn | 1664-462X |
| language | English |
| last_indexed | 2024-03-08T17:05:46Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Plant Science |
| spelling | doaj.art-40507d1d8c3a401eac673af87fc06ca92024-01-04T05:00:20ZengFrontiers Media S.A.Frontiers in Plant Science1664-462X2024-01-011410.3389/fpls.2023.12593471259347Biosynthetic pathway of prescription bergenin from Bergenia purpurascens and Ardisia japonicaXiang-Yu Liu0Xiang-Yu Liu1Yi-Na Wang2Yi-Na Wang3Jiang-Shun Du4Jiang-Shun Du5Bi-Huan Chen6Bi-Huan Chen7Kun-Yi Liu8Lei Feng9Lei Feng10Gui-Sheng Xiang11Gui-Sheng Xiang12Shuang-Yan Zhang13Shuang-Yan Zhang14Ying-Chun Lu15Sheng-Chao Yang16Sheng-Chao Yang17Guang-Hui Zhang18Guang-Hui Zhang19Bing Hao20Bing Hao21College of Agronomy and Biotechnology, National and Local Joint Engineering Research Center on Germplasm Innovation & Utilization of Chinese Medicinal Materials in Southwest China, Key Laboratory of Medicinal Plant Biology of Yunnan Province, Yunnan Agricultural University, Kunming, Yunnan, ChinaYunnan Characteristic Plant Extraction Laboratory, Kunming, Yunnan, ChinaCollege of Agronomy and Biotechnology, National and Local Joint Engineering Research Center on Germplasm Innovation & Utilization of Chinese Medicinal Materials in Southwest China, Key Laboratory of Medicinal Plant Biology of Yunnan Province, Yunnan Agricultural University, Kunming, Yunnan, ChinaYunnan Characteristic Plant Extraction Laboratory, Kunming, Yunnan, ChinaCollege of Agronomy and Biotechnology, National and Local Joint Engineering Research Center on Germplasm Innovation & Utilization of Chinese Medicinal Materials in Southwest China, Key Laboratory of Medicinal Plant Biology of Yunnan Province, Yunnan Agricultural University, Kunming, Yunnan, ChinaYunnan Characteristic Plant Extraction Laboratory, Kunming, Yunnan, ChinaCollege of Agronomy and Biotechnology, National and Local Joint Engineering Research Center on Germplasm Innovation & Utilization of Chinese Medicinal Materials in Southwest China, Key Laboratory of Medicinal Plant Biology of Yunnan Province, Yunnan Agricultural University, Kunming, Yunnan, ChinaYunnan Characteristic Plant Extraction Laboratory, Kunming, Yunnan, ChinaYunnan Characteristic Plant Extraction Laboratory, Kunming, Yunnan, ChinaCollege of Agronomy and Biotechnology, National and Local Joint Engineering Research Center on Germplasm Innovation & Utilization of Chinese Medicinal Materials in Southwest China, Key Laboratory of Medicinal Plant Biology of Yunnan Province, Yunnan Agricultural University, Kunming, Yunnan, ChinaYunnan Characteristic Plant Extraction Laboratory, Kunming, Yunnan, ChinaCollege of Agronomy and Biotechnology, National and Local Joint Engineering Research Center on Germplasm Innovation & Utilization of Chinese Medicinal Materials in Southwest China, Key Laboratory of Medicinal Plant Biology of Yunnan Province, Yunnan Agricultural University, Kunming, Yunnan, ChinaYunnan Characteristic Plant Extraction Laboratory, Kunming, Yunnan, ChinaCollege of Agronomy and Biotechnology, National and Local Joint Engineering Research Center on Germplasm Innovation & Utilization of Chinese Medicinal Materials in Southwest China, Key Laboratory of Medicinal Plant Biology of Yunnan Province, Yunnan Agricultural University, Kunming, Yunnan, ChinaYunnan Characteristic Plant Extraction Laboratory, Kunming, Yunnan, ChinaYunnan Characteristic Plant Extraction Laboratory, Kunming, Yunnan, ChinaCollege of Agronomy and Biotechnology, National and Local Joint Engineering Research Center on Germplasm Innovation & Utilization of Chinese Medicinal Materials in Southwest China, Key Laboratory of Medicinal Plant Biology of Yunnan Province, Yunnan Agricultural University, Kunming, Yunnan, ChinaYunnan Characteristic Plant Extraction Laboratory, Kunming, Yunnan, ChinaCollege of Agronomy and Biotechnology, National and Local Joint Engineering Research Center on Germplasm Innovation & Utilization of Chinese Medicinal Materials in Southwest China, Key Laboratory of Medicinal Plant Biology of Yunnan Province, Yunnan Agricultural University, Kunming, Yunnan, ChinaYunnan Characteristic Plant Extraction Laboratory, Kunming, Yunnan, ChinaYunnan Characteristic Plant Extraction Laboratory, Kunming, Yunnan, ChinaCollege of Tobacco Science, Yunnan Agricultural University, Kunming, Yunnan, ChinaBergenin is a typical carbon glycoside and the primary active ingredient in antitussive drugs widely prescribed for central cough inhibition in China. The bergenin extraction industry relies on the medicinal plant species Bergenia purpurascens and Ardisia japonica as their resources. However, the bergenin biosynthetic pathway in plants remains elusive. In this study, we functionally characterized a shikimate dehydrogenase (SDH), two O-methyltransferases (OMTs), and a C-glycosyltransferase (CGT) involved in bergenin synthesis through bioinformatics analysis, heterologous expression, and enzymatic characterization. We found that BpSDH2 catalyzes the two-step dehydrogenation process of shikimic acid to form gallic acid (GA). BpOMT1 and AjOMT1 facilitate the methylation reaction at the 4-OH position of GA, resulting in the formation of 4-O-methyl gallic acid (4-O-Me-GA). AjCGT1 transfers a glucose moiety to C-2 to generate 2-Glucosyl-4-O-methyl gallic acid (2-Glucosyl-4-O-Me-GA). Bergenin production ultimately occurs in acidic conditions or via dehydration catalyzed by plant dehydratases following a ring-closure reaction. This study for the first time uncovered the biosynthetic pathway of bergenin, paving the way to rational production of bergenin in cell factories via synthetic biology strategies.https://www.frontiersin.org/articles/10.3389/fpls.2023.1259347/fullbiosynthetic pathwaybergenincarbon glycosidesC-glycosyltransferaseO-methyltransferases |
| spellingShingle | Xiang-Yu Liu Xiang-Yu Liu Yi-Na Wang Yi-Na Wang Jiang-Shun Du Jiang-Shun Du Bi-Huan Chen Bi-Huan Chen Kun-Yi Liu Lei Feng Lei Feng Gui-Sheng Xiang Gui-Sheng Xiang Shuang-Yan Zhang Shuang-Yan Zhang Ying-Chun Lu Sheng-Chao Yang Sheng-Chao Yang Guang-Hui Zhang Guang-Hui Zhang Bing Hao Bing Hao Biosynthetic pathway of prescription bergenin from Bergenia purpurascens and Ardisia japonica Frontiers in Plant Science biosynthetic pathway bergenin carbon glycosides C-glycosyltransferase O-methyltransferases |
| title | Biosynthetic pathway of prescription bergenin from Bergenia purpurascens and Ardisia japonica |
| title_full | Biosynthetic pathway of prescription bergenin from Bergenia purpurascens and Ardisia japonica |
| title_fullStr | Biosynthetic pathway of prescription bergenin from Bergenia purpurascens and Ardisia japonica |
| title_full_unstemmed | Biosynthetic pathway of prescription bergenin from Bergenia purpurascens and Ardisia japonica |
| title_short | Biosynthetic pathway of prescription bergenin from Bergenia purpurascens and Ardisia japonica |
| title_sort | biosynthetic pathway of prescription bergenin from bergenia purpurascens and ardisia japonica |
| topic | biosynthetic pathway bergenin carbon glycosides C-glycosyltransferase O-methyltransferases |
| url | https://www.frontiersin.org/articles/10.3389/fpls.2023.1259347/full |
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