A chemical biology approach based on norflurazon inhibition of the carotenoid biosynthesis was first applied to investigate the regulation of carotenoid synthesis for enhancing lipid biosynthesis in Schizochytrium sp. The results showed that adding 100 µM norflurazon remarkably inhibited the accumulation of carotenoid, while significantly promoting fatty acid synthesis, leading to 39.76% and 29.3% increases of lipid content and DHA content, respectively. In addition, norflurazon induced a lower intracellular ROS level. LC-MS targeted metabolomics and comparative transcriptomics analysis revealed that the fatty acid synthesis and the antioxidant system were enhanced with norflurazon, which might lead to a lower ROS level and enhanced lipid content. Moreover, the competitive pathways were attenuated, including the synthesis of terpenoids and several amino acids (i.e., serine, aspartic acid, lysine, and glutamic acid) and the TCA cycle, indicating the carbon flux was directed toward fatty acid synthesis. Furthermore, the accumulation of leucine was improved, potentially contributing to the higher synthesis of fatty acids. Finally, the up-regulated genes involved in nitrogen metabolism suggested that norflurazon induced more efficient nitrogen assimilation.

基于氟虫草抑制类胡萝卜素生物合成的化学生物学方法首次应用于研究类胡萝卜素合成的调节以增强裂殖壶菌属的脂质生物合成。结果表明，添加100 μM氟虫草显着抑制了类胡萝卜素的积累，同时显着促进了脂肪酸的合成，导致脂质含量和DHA含量分别增加了39.76%和29.3%。此外，诺氟拉松诱导较低的细胞内 ROS 水平。LC-MS 靶向代谢组学比较转录组学分析显示，氟虫草增强了脂肪酸合成和抗氧化系统，这可能导致较低的 ROS 水平和较高的脂质含量。此外，竞争性途径减弱，包括萜类化合物和几种氨基酸（即丝氨酸、天冬氨酸、赖氨酸和谷氨酸）的合成和 TCA 循环，表明碳通量被导向脂肪酸合成。此外，亮氨酸的积累得到改善，可能有助于脂肪酸的更高合成。最后，参与氮代谢的上调基因表明氟虫草灵诱导了更有效的氮同化作用。