School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin 300350, Tianjin 300350, PR China.
Key Laboratory of System Bioengineering, Tianjin University , Ministry of Education, Yaguan Road 135, Jinnan District, Tianjin 300350, Tianjin 300350, PR China.
FEMS Microbiol Lett. 2022 Aug 16;369(1). doi: 10.1093/femsle/fnac070.
Taraxerol is an oleanane-type pentacyclic triterpenoid compound distributed in many plant species that has good effects on the treatment of inflammation and tumors. However, the taraxerol content in medicinal plants is low, and chemical extraction requires considerable energy and time, so taraxerol production is a problem. It is a promising strategy to produce taraxerol by applying recombinant microorganisms. In this study, a Saccharomyces cerevisiae strain WKde2 was constructed to produce taraxerol with a titer of 1.85 mg·l-1, and the taraxerol titer was further increased to 12.51 mg·l-1 through multiple metabolic engineering strategies. The endoplasmic reticulum (ER) size regulatory factor INO2, which was reported to increase squalene and cytochrome P450-mediated 2,3-oxidosqualene production, was overexpressed in this study, and the resultant strain WTK11 showed a taraxerol titer of 17.35 mg·l-1. Eventually, the highest reported titer of 59.55 mg·l-1 taraxerol was achieved in a 5 l bioreactor. These results will serve as a general strategy for the production of other triterpenoids in yeast.
蒲公英甾醇是一种广泛存在于多种植物中的五环三萜类化合物，具有良好的抗炎和抗肿瘤作用。然而，药用植物中的蒲公英甾醇含量较低，化学提取需要相当多的能量和时间，因此蒲公英甾醇的生产是一个问题。应用重组微生物生产蒲公英甾醇是一种很有前途的策略。本研究构建了一株产蒲公英甾醇的酿酒酵母 WKde2 菌株，其产量为 1.85mg·l-1，通过多种代谢工程策略，进一步将蒲公英甾醇产量提高到 12.51mg·l-1。内质网（ER）大小调节因子 INO2 被报道可增加鲨烯和细胞色素 P450 介导的 2,3-氧化鲨烯产量，本研究中过表达了 INO2，所得菌株 WTK11 的蒲公英甾醇产量为 17.35mg·l-1。最终，在 5L 生物反应器中实现了 59.55mg·l-1 蒲公英甾醇的最高报道产量。这些结果将为酵母中其他三萜类化合物的生产提供一种通用策略。
