Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering , Xiamen University , Xiamen 361005 , P.R. China.
The Key Lab for Synthetic Biotechnology of Xiamen City , Xiamen University , Xiamen 361005 , P.R. China.
J Agric Food Chem. 2018 May 30;66(21):5382-5391. doi: 10.1021/acs.jafc.8b01026. Epub 2018 May 16.
Polyunsaturated fatty acids (PUFAs) have been widely applied in the food and medical industry. In this study, malonyl-CoA: ACP transacylase (MAT) was overexpressed through homologous recombination to improve PUFA production in Schizochytrium. The results showed that the lipid and PUFA concentration were increased by 10.1 and 24.5% with MAT overexpression, respectively. Metabolomics analysis revealed that the intracellular tricarboxylic acid cycle was weakened and glucose absorption was accelerated in the engineered strain. In the mevalonate pathway, intracellular carotene content was decreased, and the carbon flux was then redirected toward PUFA synthesis. Furthermore, a glucose fed-batch fermentation was finally performed with the engineered Schizochytrium. The total lipid yield was further increased to 110.5 g/L, 39.6% higher than the wild strain. Docosahexaenoic acid and eicosapentaenoic acid yield were enhanced to 47.39 g/L and 1.65 g/L with an increase of 81.5 and 172.5%, respectively. This study provided an effective metabolic engineering strategy for industrial PUFA production.
多不饱和脂肪酸(PUFAs)已广泛应用于食品和医疗行业。在这项研究中,通过同源重组过表达丙二酰辅酶 A:ACP 转移酶(MAT),以提高裂殖壶菌中 PUFAs 的产量。结果表明,MAT 过表达使脂质和 PUFAs 浓度分别提高了 10.1%和 24.5%。代谢组学分析表明,工程菌株的细胞内三羧酸循环减弱,葡萄糖吸收加速。在甲羟戊酸途径中,细胞内类胡萝卜素含量降低,碳通量随后重新定向合成 PUFAs。最后,对工程化的裂殖壶菌进行了葡萄糖分批补料发酵。总脂产量进一步提高到 110.5 g/L,比野生型提高了 39.6%。二十二碳六烯酸和二十碳五烯酸的产量分别提高到 47.39 g/L 和 1.65 g/L,分别提高了 81.5%和 172.5%。这项研究为工业 PUFAs 生产提供了一种有效的代谢工程策略。