Metabolic Engineering for Glycyrrhetinic Acid Production in Saccharomyces cerevisiae.

Ruobing Guan,Mengge Wang,Wei Lin,Cheng-Yun Jin,Zhonghua Guan,Xiao-Jun Ji,Yongjun Wei

doi:10.3389/fbioe.2020.588255

Abstract

Glycyrrhetinic acid (GA) is one of the main bioactive components of licorice, and it is widely used in traditional Chinese medicine due to its hepatoprotective, immunomodulatory, anti-inflammatory and anti-viral functions. Currently, GA is mainly extracted from the roots of cultivated licorice. However, licorice only contains low amounts of GA, and the amount of licorice that can be planted is limited. GA supplies are therefore limited and cannot meet the demands of growing markets. GA has a complex chemical structure, and its chemical synthesis is difficult, therefore, new strategies to produce large amounts of GA are needed. The development of metabolic engineering and emerging synthetic biology provide the opportunity to produce GA using microbial cell factories. In this review, current advances in the metabolic engineering of Saccharomyces cerevisiae for GA biosynthesis and various metabolic engineering strategies that can improve GA production are summarized. Furthermore, the advances and challenges of yeast GA production are also discussed. In summary, GA biosynthesis using metabolically engineered S. cerevisiae serves as one possible strategy for sustainable GA supply and reasonable use of traditional Chinese medical plants.

Highlights

Licorice refers to the legume plant of Glycyrrhiza uralensis Fisch., Glycyrrhiza flata Bat. or Glycyrrhiza glabra L., and it is widely used in traditional herbal medicine (Asl and Hosseinzadeh, 2008)
The development of synthetic biology and metabolic engineering makes the microbial biosynthesis of Glycyrrhetinic acid (GA) possible (Wang C. et al, 2019), and microbial cell factories provide a practical and effective way to solve the problem of sustainable production of medical plant resources (Xu et al, 2020)
We summarize the current progress for GA production in S. cerevisiae and provide some future prospects for the field

Summary

Introduction

Licorice refers to the legume plant of Glycyrrhiza uralensis Fisch., Glycyrrhiza flata Bat. or Glycyrrhiza glabra L., and it is widely used in traditional herbal medicine (Asl and Hosseinzadeh, 2008). The development of synthetic biology and metabolic engineering makes the microbial biosynthesis of GA possible (Wang C. et al, 2019), and microbial cell factories provide a practical and effective way to solve the problem of sustainable production of medical plant resources (Xu et al, 2020). IPP and DMAPP have been shown to be the important intermediate products of this process, and they are the precursors for terpenoids synthesis in plant cells (Wang Q. et al, 2019).

Results

Conclusion