A Yarrowia lipolytica strain engineered for arachidonic acid production counteracts metabolic burden by redirecting carbon flux towards intracellular fatty acid accumulation at the expense of organic acids secretion
A Yarrowia lipolytica strain engineered for arachidonic acid production counteracts metabolic burden by redirecting carbon flux towards intracellular fatty acid accumulation at the expense of organic acids secretion
复制标题
一种专为生产花生四烯酸而设计的解脂耶氏酵母菌株，通过将碳通量重新导向细胞内脂肪酸积累（以牺牲有机酸分泌为代价）来抵消代谢负担
DOI：
10.1016/j.bej.2017.10.007
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发表时间：
2017-12-15
影响因子：
3.9
通讯作者：
Ji, Xiao-Jun
中科院分区：
文献类型：
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作者：
Liu, Hu-Hu;Zeng, Si-Yu;Ji, Xiao-Jun
合成多基因途径使微生物能够合成新的产物，但通常会影响细胞生长。在我们之前的研究中，在解脂耶氏酵母中构建了花生四烯酸生物合成途径，有趣的是，工程菌株在没有代谢负担的情况下实现了更高的生物量生产。在这项研究中，我们提供了一个深入的分析，这多基因途径对Y。解脂与出发菌株相比，工程菌能够产生花生四烯酸（占总脂肪酸的0.42%）。此外，工程菌生长健壮，胞外有机酸滴度低。ciRT-PCR分析结果表明，异源代谢途径影响了脂肪酸代谢相关基因的表达和有机酸的分泌。综上所述，因此可以得出结论，合成代谢途径能够以Y中胞外有机酸分泌为代价将碳通量重定向到细胞内脂肪酸积累。解脂菌，这是非常可取的，并有希望在其他菌株中复制。(C)2017爱思唯尔B. V.保留所有权利。
Synthetic multigene pathways enable microbes to synthesize novel products, but generally affect cell growth. In our previous study, an arachidonic acid biosynthesis pathway was constructed in Yarrowia lipolytica, and interestingly, the engineered strain achieved higher biomass production without metabolic burden. In this study, we provide an in-depth analysis of the effects of this multigene pathway on Y. lipolytica. Compared to the original strain, the engineered strain was able to produce arachidonic acid (0.42% of total fatty acids). Moreover, the engineered strain had robust growth and a low titer of extracellular organic acids. ciRT-PCR analysis results indicated that the heterologous metabolic pathway influenced the expression of genes related to fatty acid metabolism and the secretion of organic acids. Taken together, it can thus be concluded that the synthetic metabolic pathway is able to redirect the carbon flux towards intracellular fatty acid accumulation at the expense of extracellular organic acid secretion in Y. lipolytica, which is highly desirable and can hopefully be copied in other strains. (C) 2017 Elsevier B.V. All rights reserved.