Sun Wen-Zhuo, Wang Xin, Fu Meng-Yu, Liu Le-Fan, Zhang Ping, Yin Bin-Cheng, Liu Wei-Bing, Ye Bang-Ce
Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
ACS Synth Biol. 2025 Apr 18;14(4):1142-1151. doi: 10.1021/acssynbio.4c00754. Epub 2025 Mar 19.
Icaritin (ICT) is a naturally occurring flavonoid compound with notable anticancer properties, recently recognized for its efficacy in treating advanced hepatic carcinoma. Traditional methods of ICT production, including plant extraction and chemical synthesis, face challenges such as low yield and environmental concerns. This study leverages synthetic biology to construct a microbial cell factory using for de novo ICT synthesis. We engineered the yeast by integrating the ICT synthesis pathway involving EsPT from and OsOMTm from . By optimizing the metabolic pathways, including enhancing the supply of DMAPP via mevalonate pathway modifications, and fine-tuning the expression and catalytic efficiency of EsPT through truncation strategies, we significantly improved ICT yield to 247.02 mg/L─the highest microbial ICT titer reported to date. These findings lay a solid foundation for the large-scale industrial production of ICT and offer valuable insights into the biosynthesis of other flavonoid plant natural products.
淫羊藿苷（ICT）是一种天然存在的具有显著抗癌特性的黄酮类化合物，最近因其在治疗晚期肝癌方面的功效而受到认可。传统的ICT生产方法，包括植物提取和化学合成，面临着产量低和环境问题等挑战。本研究利用合成生物学构建了一个用于从头合成ICT的微生物细胞工厂。我们通过整合来自[具体来源1]的EsPT和来自[具体来源2]的OsOMTm的ICT合成途径对酵母进行了工程改造。通过优化代谢途径，包括通过甲羟戊酸途径修饰增强DMAPP的供应，并通过截短策略微调EsPT的表达和催化效率，我们将ICT产量显著提高到247.02 mg/L，这是迄今为止报道的最高微生物ICT滴度。这些发现为ICT的大规模工业生产奠定了坚实基础，并为其他黄酮类植物天然产物的生物合成提供了有价值的见解。
