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Unravelling and reconstructing the biosynthetic pathway of bergenin

Author

Listed:
  • Ruiqi Yan

    (Minzu University of China)

  • Binghan Xie

    (Minzu University of China)

  • Kebo Xie

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs
    NHC Key Laboratory of Biosynthesis of Natural Products)

  • Qi Liu

    (Minzu University of China)

  • Songyang Sui

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs
    NHC Key Laboratory of Biosynthesis of Natural Products)

  • Shuqi Wang

    (Minzu University of China)

  • Dawei Chen

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs
    NHC Key Laboratory of Biosynthesis of Natural Products)

  • Jimei Liu

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs
    NHC Key Laboratory of Biosynthesis of Natural Products)

  • Ridao Chen

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs
    NHC Key Laboratory of Biosynthesis of Natural Products)

  • Jungui Dai

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs
    NHC Key Laboratory of Biosynthesis of Natural Products)

  • Lin Yang

    (Minzu University of China)

Abstract

Bergenin, a rare C-glycoside of 4-O-methyl gallic acid with pharmacological properties of antitussive and expectorant, is widely used in clinics to treat chronic tracheitis in China. However, its low abundance in nature and structural specificity hampers the accessibility through traditional crop-based manufacturing or chemical synthesis. In the present work, we elucidate the biosynthetic pathway of bergenin in Ardisia japonica by identifying the highly regio- and/or stereoselective 2-C-glycosyltransferases and 4-O-methyltransferases. Then, in Escherichia coli, we reconstruct the de novo biosynthetic pathway of 4-O-methyl gallic acid 2-C-β-D-glycoside, which is the direct precursor of bergenin and is conveniently esterified into bergenin by in situ acid treatment. Moreover, further metabolic engineering improves the production of bergenin to 1.41 g L−1 in a 3-L bioreactor. Our work provides a foundation for sustainable supply of bergenin and alleviates its resource shortage via a synthetic biology approach.

Suggested Citation

  • Ruiqi Yan & Binghan Xie & Kebo Xie & Qi Liu & Songyang Sui & Shuqi Wang & Dawei Chen & Jimei Liu & Ridao Chen & Jungui Dai & Lin Yang, 2024. "Unravelling and reconstructing the biosynthetic pathway of bergenin," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47502-2
    DOI: 10.1038/s41467-024-47502-2
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    References listed on IDEAS

    as
    1. Prashanth Srinivasan & Christina D. Smolke, 2020. "Biosynthesis of medicinal tropane alkaloids in yeast," Nature, Nature, vol. 585(7826), pages 614-619, September.
    2. Kebo Xie & Xiaolin Zhang & Songyang Sui & Fei Ye & Jungui Dai, 2020. "Exploring and applying the substrate promiscuity of a C-glycosyltransferase in the chemo-enzymatic synthesis of bioactive C-glycosides," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    3. Ryan S. Nett & Warren Lau & Elizabeth S. Sattely, 2020. "Discovery and engineering of colchicine alkaloid biosynthesis," Nature, Nature, vol. 584(7819), pages 148-153, August.
    4. Xiaonan Liu & Jian Cheng & Guanghui Zhang & Wentao Ding & Lijin Duan & Jing Yang & Ling Kui & Xiaozhi Cheng & Jiangxing Ruan & Wei Fan & Junwen Chen & Guangqiang Long & Yan Zhao & Jing Cai & Wen Wang , 2018. "Engineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    5. Ryan S. Nett & Warren Lau & Elizabeth S. Sattely, 2020. "Publisher Correction: Discovery and engineering of colchicine alkaloid biosynthesis," Nature, Nature, vol. 584(7821), pages 35-35, August.
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