Deciphering and regulating carotenoid synthesis using norflurazon to enhance fatty acid synthesis in oleaginous marine protist Schizochytrium sp. S31

Abstract

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.