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

Ke Xu, Yu jia Zhao, Nadeem Ahmad, Jing nan Wang, Bo Lv*, Ying Wang, Jun Ge, Chun Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalSynthetic and Systems Biotechnology
Volume6
Issue number3
DOIs
Publication statusPublished - Sept 2021

Keywords

  • Glycyrrhetic Acid 3-O-mono-β-D-glucuronide(GAMG)
  • Glycyrrhizin (GL)
  • Homo sapiens
  • O-glycosyltransferase
  • Saccharomyces cerevisiae

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