A highly selective <i>C</i>-rhamnosyltransferase from <i>Viola tricolor</i> and insights into its mechanisms.

Bo-yun Han; Zi-long Wang; Junhao LI; Qing Jin; Hao-tian Wang; Kuan Chen; Yang YI; Hans Ågren; Xue Qiao; Min YE

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A highly selective C-rhamnosyltransferase from Viola tricolor and insights into its mechanisms.

Author: Bo-Yun HAN ¹ ; Zi-Long WANG ¹ ; Junhao LI ² ; Qing JIN ¹ ; Hao-Tian WANG ¹ ; Kuan CHEN ¹ ; Yang YI ¹ ; Hans ÅGREN ² ; Xue QIAO ¹ ; Min YE ¹
Author Information

1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
2. Department of Physics and Astronomy, Uppsala University, Uppsala SE-751 20, Sweden.
Publication Type:Journal Article
Keywords: Biosynthesis; C-rhamnosyltransferase; Catalytic mechanisms; Flavonoid C-glycoside; Sugar donor selectivity
From: Acta Pharmaceutica Sinica B 2023;13(8):3535-3544
CountryChina
Language:English
Abstract: C-Glycosides are important natural products with various bioactivities. In plant biosynthetic pathways, the C-glycosylation step is usually catalyzed by C-glycosyltransferases (CGTs), and most of them prefer to accept uridine 5'-diphosphate glucose (UDP-Glc) as sugar donor. No CGTs favoring UDP-rhamnose (UDP-Rha) as sugar donor has been reported, thus far. Herein, we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola tricolor. VtCGTc could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside, and exhibited high selectivity towards UDP-Rha. Mechanisms for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics (MD) simulations and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) binding free energy calculations. Val144 played a vital role in recognizing UDP-Rha, and the V144T mutant could efficiently utilize UDP-Glc. This work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.