Cheng Jintao, Pu Zhongji, Chen Jiali, Chen Dingfeng, Li Baoxian, Wen Zhengshun, Jin Yuanxiang, Yao Yanlai, Shao Kan, Gu Xiaosong, Yang Guiling
Xianghu Laboratory, Hangzhou, 310027, China.
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China.
Synth Syst Biotechnol. 2024 Sep 17;10(1):120-126. doi: 10.1016/j.synbio.2024.09.006. eCollection 2025.
(-)-α-Bisabolol is a plant-derived sesquiterpene derived from which can be used as a raw material in cosmetics and has anti-inflammatory function. In this study, we designed six mutation sites of the (-)-α-bisabolol synthase BOS using the plmDCA algorithm. Among these, the F324Y mutation demonstrated exceptional performance, increasing the product yield by 73 %. We constructed a (-)-α-bisabolol biosynthesis pathways through systematic synthetic biology strategies, including the enzyme design of BOS, selection of different linkers in fusion expression, and optimization of the mevalonate pathway, weakening the branching metabolic flow and multi-copy strategies, the yield of (-)-α-bisabolol was significantly increased, which was nearly 35-fold higher than that of the original strain (2.03 mg/L). The engineered strain was capable of producing 69.7 mg/L in shake flasks. To the best of our knowledge, this is the first report on the biosynthesis of (-)-α-bisabolol in , implying this is a robust cell factory for sustainable production of other terpenoids.
（-）-α-红没药醇是一种源自植物的倍半萜，可用作化妆品原料，具有抗炎功能。在本研究中，我们使用plmDCA算法设计了（-）-α-红没药醇合酶BOS的六个突变位点。其中，F324Y突变表现出卓越性能，使产物产量提高了73%。我们通过系统的合成生物学策略构建了（-）-α-红没药醇生物合成途径，包括BOS的酶设计、融合表达中不同接头的选择、甲羟戊酸途径的优化、削弱分支代谢流和多拷贝策略，（-）-α-红没药醇的产量显著提高，比原始菌株（2.03mg/L）高出近35倍。该工程菌株在摇瓶中能够产生69.7mg/L。据我们所知，这是关于在[具体生物名称未给出]中生物合成（-）-α-红没药醇的首次报道，意味着这是用于可持续生产其他萜类化合物的强大细胞工厂。
