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 ± 4.6 mg/L and 18.9 ± 2.0 mg/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.

甘草次酸（GA）及其前体11-氧代-β-淀粉状糖蛋白是甘草根中的典型三萜类化合物，甘草是一种具有多种功能和生理作用的传统中草药。在这项研究中，我们为酿酒酵母中的GA和11-氧代-β-amyrin的合成开发了一种新颖而高效的途径通过引入有效的细胞色素P450（CYP450：Uni25647和CYP72A63），并通过转录组和全基因组筛选和鉴定，将豆科植物的还原系统配对。通过增加Uni25647的拷贝数并配对来自各种植物来源的细胞色素P450还原酶（CPR），将11-氧代-β-amyrin和GA的滴度提高至108.1±4.6 mg / L和18.9±2.0 mg / L，与先前报道的数据相比，分别高出近1422倍和946.5倍。据我们所知，这些是酿酒酵母中GA和11-氧代-β-amyrin的最高滴度，表明在不破坏甘草植物或土壤的情况下获得增加的GA及其相关三萜类化合物的令人鼓舞和有希望的方法生态系统。