Unravelling and reconstructing the biosynthetic pathway of bergenin.
Nat Commun
; 15(1): 3539, 2024 Apr 26.
Article
em En
| MEDLINE
| ID: mdl-38670975
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-ß-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzopiranos
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Escherichia coli
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Vias Biossintéticas
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Engenharia Metabólica
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article