Feng Pan, Sun Bowen, Bi Haoran, Bao Yufei, Wang Meng, Zhang Huili, Fang Yunming
College of Chemical Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029, PR China.
National Energy R&D Center of Biorefinery, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, PR China.
ACS Synth Biol. 2025 Apr 18;14(4):1129-1141. doi: 10.1021/acssynbio.4c00728. Epub 2025 Mar 3.
α-Bisabolene's distinctive aroma is highly prized in fragrances and cosmetics, while its antioxidant properties hold significant pharmaceutical potential. However, the production of α-bisabolene in remains an outstanding challenge due to cell growth limitations and insufficient supply of the α-bisabolene precursor farnesyl pyrophosphate. In this work, a new platform strain capable of producing high levels of α-bisabolene was presented. Carbon flux in the α-bisabolene synthesis pathway was maximized by iterative enhancement of the mevalonate metabolic pathway. The effects of MVA pathway intermediates on cell growth were addressed through a two-stage fermentation controlled based on a temperature-sensitive regulation strategy. The fermentation medium was optimized based on metabolomics and response surface model analysis. Under the optimal fermentation process, the titer of α-bisabolene reached 18.6 g/L during fed-batch fermentation, representing the highest titer reported to date. These strategies open up new avenues for industrial-scale terpene biosynthesis.
α-红没药烯独特的香气在香料和化妆品中备受青睐，而其抗氧化特性具有显著的药用潜力。然而，由于细胞生长限制以及α-红没药烯前体法呢基焦磷酸供应不足，α-红没药烯的生产仍然是一个突出的挑战。在这项工作中，提出了一种能够高产α-红没药烯的新型平台菌株。通过迭代增强甲羟戊酸代谢途径，使α-红没药烯合成途径中的碳通量最大化。基于温度敏感调控策略的两阶段发酵控制解决了甲羟戊酸途径中间体对细胞生长的影响。基于代谢组学和响应面模型分析对发酵培养基进行了优化。在最佳发酵过程中，补料分批发酵时α-红没药烯的产量达到18.6 g/L，这是迄今为止报道的最高产量。这些策略为工业规模的萜类生物合成开辟了新途径。
