Unravelling and reconstructing the biosynthetic pathway of bergenin

Ruiqi Yan, Binghan Xie, Kebo Xie (), Qi Liu, Songyang Sui, Shuqi Wang, Dawei Chen, Jimei Liu, Ridao Chen, Jungui Dai () and Lin Yang ()
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Ruiqi Yan: Minzu University of China
Binghan Xie: Minzu University of China
Kebo Xie: Chinese Academy of Medical Sciences & Peking Union Medical College
Qi Liu: Minzu University of China
Songyang Sui: Chinese Academy of Medical Sciences & Peking Union Medical College
Shuqi Wang: Minzu University of China
Dawei Chen: Chinese Academy of Medical Sciences & Peking Union Medical College
Jimei Liu: Chinese Academy of Medical Sciences & Peking Union Medical College
Ridao Chen: Chinese Academy of Medical Sciences & Peking Union Medical College
Jungui Dai: Chinese Academy of Medical Sciences & Peking Union Medical College
Lin Yang: Minzu University of China

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47502-2

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