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O-glycosyltransferases from Homo sapiens contributes to the biosynthesis of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide and Glycyrrhizin in Saccharomyces cerevisiae 被引量:6
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作者 Ke Xu Yu-jia Zhao +5 位作者 Nadeem Ahmad jing-nan wang Bo Lv Ying wang Jun Ge Chun Li 《Synthetic and Systems Biotechnology》 SCIE 2021年第3期173-179,共7页
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 phar... 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. 展开更多
关键词 O-glycosyltransferase Homo sapiens Glycyrrhizin(GL) Saccharomyces cerevisiae Glycyrrhetic Acid 3-O-mono-β-D-glucuronide(GAMG)
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