Surveying the lipogenesis landscape in Yarrowia lipolytica through understanding the function of a Mga2p regulatory protein mutant
Surveying the lipogenesis landscape in Yarrowia lipolytica through understanding the function of a Mga2p regulatory protein mutant
复制标题
DOI：
10.1016/j.ymben.2015.07.004
复制
发表时间：
2015-09-01
影响因子：
8.4
通讯作者：
Alper, Hal S.
中科院分区：
文献类型：
--
作者：
Liu, Leqian;Markham, Kelly;Alper, Hal S.
产脂生物代表了油脂化学生产代谢工程的重要起点。虽然先前的工程努力能够显著改善解脂耶氏酵母中的脂质产生，但脂肪生成景观，特别是关于调控元件，尚未得到充分探索。通过比较基因组学和转录组学的方法，我们确定并验证了突变的mga 2蛋白，作为去饱和酶基因表达和有效的脂肪生成因子的调节剂。所得菌株富含不饱和脂肪酸。将这种突变体的潜在机制与其他先前工程化的菌株进行比较表明，当与脂肪酸催化剂过度表达结合时，在糖酵解和TCA循环之间产生不平衡可以作为脂肪生成的驱动力。进一步的比较转录组学分析揭示了与这些不同基因型相关的不同和会聚的重新布线。最后，通过组合代谢工程靶标，可以将含有突变型mga 2基因的菌株进一步工程化至25 g/L的脂质生产滴度。(C)2015年国际代谢工程学会。爱思唯尔公司出版All rights reserved.
Lipogenic organisms represent great starting points for metabolic engineering of oleochemical production. While previous engineering efforts were able to significantly improve lipid production in Yarrovvia lipolytica, the lipogenesis landscape, especially with respect to regulatory elements, has not been fully explored. Through a comparative genomics and transcriptomics approach, we identified and validated a mutant mga2 protein that serves as a regulator of desaturase gene expression and potent lipogenesis factor. The resulting strain is enriched in unsaturated fatty acids. Comparing the underlying mechanism of this mutant to other previously engineered strains suggests that creating an imbalance between glycolysis and the TCA cycle can serve as a driving force for lipogenesis when combined with fatty acid catabolism overexpressions. Further comparative transcriptomics analysis revealed both distinct and convergent rewiring associated with these different genotypes. Finally, by combining metabolic engineering targets, it is possible to further engineer a strain containing the mutant mga2 gene to a lipid production titer of 25 g/L. (C) 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.