Table_1_Metabolic Engineering for Glycyrrhetinic Acid Production in Saccharomyces cerevisiae.docx

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.

甘草次酸（Glycyrrhetinic acid，GA）是甘草的主要生物活性成分之一，因其具备保肝、免疫调节、抗炎及抗病毒的功效，被广泛应用于传统中药领域。目前，甘草次酸主要从栽培甘草的根部提取。然而，甘草中天然甘草次酸含量较低，且可种植的甘草资源总量有限，因此甘草次酸的市场供应受限，无法满足日益增长的市场需求。甘草次酸化学结构复杂，化学合成难度较高，因此亟需开发可大规模生产甘草次酸的全新策略。代谢工程与新兴合成生物学技术的发展，为利用微生物细胞工厂生产甘草次酸提供了可行机遇。本综述系统总结了当前代谢工程改造酿酒酵母（Saccharomyces cerevisiae）用于甘草次酸生物合成的研究进展，以及各类可提升甘草次酸产量的代谢工程策略。此外，本文还探讨了利用酿酒酵母生产甘草次酸的研究进展与面临的挑战。综上，利用代谢工程改造的酿酒酵母进行甘草次酸生物合成，是实现甘草次酸可持续供应、合理利用传统药用植物资源的可行途径之一。