O-glycosyltransferases from Homo sapiens contributes to the biosynthesis of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide and Glycyrrhizin in Saccharomyces cerevisiae  

作　　者：Ke Xu Yu-jia Zhao Nadeem Ahmad Jing-nan Wang Bo Lv Ying Wang Jun Ge Chun Li 

机构地区：[1]Key Lab for Industrial Biocatalysis,Ministry of Education,Department of Chemical Engineering,Tsinghua University,Beijing,100084,PR China [2]Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering,Ministry of Industry and Information Technology,Institute of Biochemical Engineering,School of Chemistry and Chemical Engineering,Beijing Institute of Technology,Beijing,100081,PR China [3]Beijing Institute of Metrology,Beijing,100029,PR China [4]Tangshan Key Laboratory of Agricultural Pathogenic Fungi and Toxins,Department of Life Science,Tangshan Normal University,Tangshan,063000,PR China [5]School of Pharmacy,Tsinghua University,Beijing,100084,PR China

出　　处：《Synthetic and Systems Biotechnology》2021年第3期173-179,共7页合成和系统生物技术（英文）

基　　金：supported by the National Key Research and Development Program of China(2018YFA0901800);the Key Research and Development Program of Hebei Province(21374301D);the Natural Science Foundation of China(No.22078171);the Natural Science Foundation of Hebei Province(No.C2019105055);the Scientific Research Foundation of Tangshan Normal University(No.2021B34).

摘　　要：Glycyrrhizin(GL)and Glycyrrhetic Acid 3-O-mono-β-D-glucuronide(GAMG)are the typical triterpenoid glycosides found in the root of licorice,a popular medicinal plant that exhibits diverse physiological effects and pharmacological manifestations.However,only few reports are available on the glycosylation enzymes involved in the biosynthesis of these valuable compounds with low conversion yield so far.In mammals,glycosyltransferases are involved in the phase II metabolism and may provide new solutions for us to engineer microbial strains to produce high valued compounds due to the substrate promiscuity of these glycosyltransferases.In this study,we mined the genomic databases of mammals and evaluated 22 candidate genes of O-glycosyltransferases by analyzing their catalytic potential for O-glycosylation of the native substrate,glycyrrhetinic acid(GA)for its glycodiversification.Out of 22 selected glycosyltransferases,only UGT1A1 exhibited high catalytic performance for biosynthesis of the key licorice compounds GL and GAMG.Molecular docking results proposed that the enzymatic activity of UGT1A1 was likely owing to the stable hydrogen bonding interactions and favorite conformations between the amino acid residues around substrate channels(P82~R85)and substrates.Furthermore,the complete biosynthesis pathway of GL was reconstructed in Saccharomyces cerevisiae for the first time,resulting in the production of 5.98±0.47 mg/L and 2.31±0.21 mg/L of GL and GAMG,respectively.

关 键 词：O-glycosyltransferase Homo sapiens Glycyrrhizin(GL) Saccharomyces cerevisiae Glycyrrhetic Acid 3-O-mono-β-D-glucuronide(GAMG) 

分 类 号：Q5[生物学—生物化学]