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Time-resolved multi-omics analysis reveals the role of nutrient stress-induced resource reallocation for TAG accumulation in oleaginous fungus Mortierella alpina.
Biotechnology for Biofuels ( IF 6.3 ) Pub Date : 2020-07-01 , DOI: 10.1186/s13068-020-01757-1
Hengqian Lu 1, 2 , Haiqin Chen 1, 2, 3, 4 , Xin Tang 1, 2 , Qin Yang 1, 2 , Hao Zhang 1, 2, 4 , Yong Q Chen 1, 2, 3, 5 , Wei Chen 1, 2, 3, 6
Affiliation  

Global resource reallocation is an established critical strategy through which organisms deal with environmental stress. The regulation of intracellular lipid storage or utilization is one of the most important strategies for maintaining energy homeostasis and optimizing growth. Oleaginous microorganisms respond to nitrogen deprivation by inducing lipid hyper accumulation; however, the associations between resource allocation and lipid accumulation are poorly understood. Here, the time-resolved metabolomics, lipidomics, and proteomics data were generated in response to nutrient availability to examine how metabolic alternations induced by nitrogen deprivation drive the triacylglycerols (TAG) accumulation in M. alpina. The subsequent accumulation of TAG under nitrogen deprivation was a consequence of the reallocation of carbon, nitrogen sources, and lipids, rather than an up-regulation of TAG biosynthesis genes. On one hand, nitrogen deprivation induced the down-regulation of isocitrate dehydrogenase level in TCA cycle and redirected glycolytic flux of carbon from amino acid biosynthesis into fatty acids’ synthesis; on the other hand, nitrogen deprivation induced the up-regulation of cell autophagy and ubiquitin-mediated protein proteolysis which resulted in a recycling of preformed protein nitrogen and carbon. Combining with the up-regulation of glutamate decarboxylase and succinic semialdehyde dehydrogenase in GABA shunt, and the phosphoenolpyruvate carboxykinase in the central hub involving pyruvate/phosphoenolpyruvate/oxaloacetate, the products from nitrogen-containing compounds degradation were recycled to be intermediates of TCA cycle and be shunted toward de novo biosynthesis of fatty acids. We found that nitrogen deprivation increased the protein level of phospholipase C/D that contributes to degradation of phosphatidylcholine and phosphatidylethanolamine, and supplied acyl chains for TAG biosynthesis pathway. In addition, ATP from substrate phosphorylation was presumed to be a critical factor regulation of the global resource allocation and fatty acids’ synthesis rate. The present findings offer a panoramic view of resource allocation by M. alpina in response to nutrient stress and revealed a set of intriguing associations between resource reallocation and TAG accumulation. This system-level insight provides a rich resource with which to explore in-depth functional characterization and gain information about the strategic combination of strain development and process integration to achieve optimal lipid productivity under nutrient stress.

中文翻译:

时间分辨多组学分析揭示了营养胁迫诱导的资源重新分配对产油真菌高山被孢霉中 TAG 积累的作用。

全球资源重新分配是生物体应对环境压力的既定关键策略。细胞内脂质储存或利用的调节是维持能量稳态和优化生长的最重要策略之一。产油微生物通过诱导脂质过度积累来应对氮缺乏;然而,人们对资源分配和脂质积累之间的关联知之甚少。在这里,时间分辨的代谢组学、脂质组学和蛋白质组学数据是根据营养可用性生成的,以检查由氮剥夺引起的代谢变化如何驱动高山葡萄中的甘油三酯 (TAG) 积累。随后在缺氮条件下 TAG 的积累是碳、氮源重新分配的结果,和脂质,而不是 TAG 生物合成基因的上调。一方面,缺氮导致三羧酸循环中异柠檬酸脱氢酶水平的下调,并将氨基酸生物合成中碳的糖酵解通量重定向到脂肪酸的合成中;另一方面,氮剥夺诱导细胞自噬和泛素介导的蛋白质蛋白水解的上调,从而导致预先形成的蛋白质氮和碳的再循环。结合 GABA 分流中谷氨酸脱羧酶和琥珀酸半醛脱氢酶的上调,以及涉及丙酮酸/磷酸烯醇丙酮酸/草酰乙酸的中央枢纽中的磷酸烯醇丙酮酸羧激酶,含氮化合物降解的产物被回收作为 TCA 循环的中间体,并被分流到脂肪酸的从头生物合成。我们发现氮剥夺增加了磷脂酶 C/D 的蛋白质水平,这有助于磷脂酰胆碱和磷脂酰乙醇胺的降解,并为 TAG 生物合成途径提供了酰基链。此外,底物磷酸化产生的 ATP 被认为是调节全球资源分配和脂肪酸合成速率的关键因素。目前的研究结果提供了 M. alpina 响应营养压力的资源分配的全景图,并揭示了资源重新分配和 TAG 积累之间的一系列有趣关联。
更新日期:2020-07-01
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