Wang Xiuwen, Mohamed Hassan, Bao Yonghong, Wu Chen, Shi Wenyue, Song Yuanda, Yang Junhuan
Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo, China.
Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Assiut, Egypt.
Front Microbiol. 2021 Nov 19;12:774825. doi: 10.3389/fmicb.2021.774825. eCollection 2021.
The fungus, , is of great interest for microbial lipids, because of its ability to accumulate intracellular lipid using various carbon sources. The biosynthesis of fatty acid requires the reducing power NADPH, and acetyl-CoA, which is produced by the cleavage of citrate in cytosol. In this study, we employed different strategies to increase lipid accumulation in the low lipid-producing fungi via metabolic engineering technology. Hence, we constructed the engineered strain of CBS 277.49 by using malate transporter () and 2-oxoglutarate: malate antiporter ( from WJ11. In comparison with the control strain, the lipid content of the overexpressed strains of and genes were increased by 24.6 and 33.8%, respectively. These results showed that and can affect the distribution of malate in mitochondria and cytosol, provide the substrates for the synthesis of citrate in the mitochondria, and accelerate the transfer of citrate from mitochondria to cytosol, which could play a significant regulatory role in fatty acid synthesis leading to lipids over accumulation.
该真菌，由于其能够利用各种碳源积累细胞内脂质，因此在微生物脂质方面具有极大的研究价值。脂肪酸的生物合成需要还原力NADPH以及乙酰辅酶A，乙酰辅酶A是由细胞质中柠檬酸的裂解产生的。在本研究中，我们采用了不同策略，通过代谢工程技术在低脂质产生的真菌中增加脂质积累。因此，我们利用苹果酸转运蛋白（）和2-氧代戊二酸：苹果酸反向转运蛋白（来自WJ11）构建了CBS 277.49的工程菌株。与对照菌株相比，和基因过表达菌株的脂质含量分别增加了24.6%和33.8%。这些结果表明，和可以影响苹果酸在线粒体和细胞质中的分布，为线粒体中柠檬酸的合成提供底物，并加速柠檬酸从线粒体向细胞质的转移，这可能在脂肪酸合成导致脂质过度积累中发挥重要的调节作用。
