Boosting 11-oxo-β-amyrin and glycyrrhetinic acid synthesis in Saccharomyces cerevisiae via pairing novel oxidation and reduction system from legume plants

  • Metab Eng. 2018 Jan;45:43-50. doi: 10.1016/j.ymben.2017.11.009.
Ming Zhu  1 ,  Caixia Wang  2 ,  Wentao Sun  3 ,  Anqi Zhou  3 ,  Ying Wang  3 ,  Genlin Zhang  2 ,  Xiaohong Zhou  3 ,  Yixin Huo  3 ,  Chun Li  4
Affiliations
  • 1. Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
  • 2. Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi, Xinjiang 832003, China.
  • 3. Institute for Biotransformation and Synthetic Biosystem/Department of Biological Engineering, School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
  • 4. Institute for Biotransformation and Synthetic Biosystem/Department of Biological Engineering, School of Life Science, Beijing Institute of Technology, Beijing 100081, China. Electronic address: [email protected].
PMID: 29196123 DOI: 10.1016/j.ymben.2017.11.009
Abstract

Glycyrrhetinic acid (GA) and its precursor, 11-oxo-β-amyrin, are typical triterpenoids found in the roots of licorice, a traditional Chinese medicinal herb that exhibits diverse functions and physiological effects. In this study, we developed a novel and highly efficient pathway for the synthesis of GA and 11-oxo-β-amyrin in Saccharomyces cerevisiae by introducing efficient cytochrome P450s (CYP450s: Uni25647 and CYP72A63) and pairing their reduction systems from legume Plants through transcriptome and genome-wide screening and identification. By increasing the copy number of Uni25647 and pairing Cytochrome P450 reductases (CPRs) from various plant sources, the titers of 11-oxo-β-amyrin and GA were increased to 108.1 ± 4.6mg/L and 18.9 ± 2.0mg/L, which were nearly 1422-fold and 946.5-fold higher, respectively, compared with previously reported data. To the best of our knowledge, these are the highest titers reported for GA and 11-oxo-β-amyrin from S. cerevisiae, indicating an encouraging and promising approach for obtaining increased GA and its related triterpenoids without destroying the licorice plant or the soil ecosystem.

Keywords
11-oxo-β-amyrin; Cytochrome P450 (CYP450); Cytochrome P450 reductase (CPR); Glycyrrhetinic acid (GA); Licorice root; Saccharomyces cerevisiae.
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