Structural mechanism of a dual-functional enzyme Dgp A/B/C as both a C-glycoside cleaving enzyme and an O-to C-glycoside isomerase  

作　　者：Pengfei He Sha Wang Sen Li Siqi Liu Shuqi Zhou Jing Wang Jiayue Tao Dongdong Wang Rufeng Wang Wenfu Ma 

机构地区：[1]School of Life Science,Beijing University of Chinese Medicine,Beijing 102488,China [2]DP Technology,Bejing 100080,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第1期246-255,共10页药学学报（英文版）

基　　金：supported by grants from National Natural Science Foundation of China(No.81073018 and 81274044)to Rufeng Wang;Startup fund program at Beijing University of Chinese Medicine(90011451310011);key research fund for drug discovery in Chinese medicine at Beijing University of Chinese Medicine(1000061223476)to Wenfu Ma。

摘　　要：The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature.The knowledge of C-glycoside breakdown and synthesis is very limited.Recently,the enzyme Dgp A/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin(daidzein-8-C-glucoside).Here we investigated how puerarin is recognized and oxidized by Dgp A based on crystal structures of Dgp A with or without substrate and biochemical characterization.More strikingly,we found that apart from being a C-glycoside cleaving enzyme,Dgp A/B/C is capable of efficiently converting O-to C-glycoside showing the activity as a structure isomerase.A possible mechanistic model was proposed dependently of the simulated complex structure of Dgp B/C with 3’’-oxo-daidzin and structure-based mutagenesis.Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation,but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.

关 键 词：C-GLYCOSIDE O-Glycoside C-Glycoside cleaving enzyme ISOMERASE Gut microbiota Flavonoid Puerarin and oxidoreductase 

分 类 号：TQ460.1[化学工程—制药化工]