Conservation of the metabolomic response to starvation across two divergent microbes

Conservation of the metabolomic response to starvation across two divergent microbes
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DOI:
10.1073/pnas.0609508103
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发表时间:
2006-12-19
影响因子:
11.1
通讯作者:
Rabinowitz, Joshua D.
Rabinowitz, Joshua D.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Brauer, Matthew J.;Yuan, Jie;Rabinowitz, Joshua D.

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我们遵循了69细胞代谢产物后,大肠杆菌和酿酒酵母的碳或氮饥饿,使用过滤培养方法,允许指数增长,非破坏性的营养去除,代谢和快速淬火。通过液相色谱-串联质谱法测量动态浓度变化,并以聚类热图格式查看。观察到文献中代谢物特异性实验预期的主要代谢反应以及许多新反应。当数据进行了分析,奇异值分解,发现两个占主导地位的特征向量,一个对应于一个通用的饥饿反应和另一个营养特定的饥饿反应,是在这两种生物体相似。这些共同捕获了完整数据集中72%的代谢物浓度变化。由通用饥饿响应载体(42%)描述的响应包括例如大多数生物合成中间体的耗尽。营养素特异性载体(30%)包括关键反应,例如增加的磷酸烯醇丙酮酸信号传导葡萄糖剥夺和增加的α-酮戊二酸信号传导氨剥夺。生物体之间的代谢相似性从代谢的共价反应网络扩展到包括对营养剥夺的代谢组反应的许多元素。
We followed 69 cellular metabolites after carbon or nitrogen starvation of Escherichia coli and Saccharomyces cerevisiae, using a filter-culture methodology that allows exponential growth, nondisruptive nutrient removal, and fast quenching of metabolism. Dynamic concentration changes were measured by liquid chromatography-tandem mass spectrometry and viewed in clustered heat-map format. The major metabolic responses anticipated from metabolite-specific experiments in the literature were observed as well as a number of novel responses. When the data were analyzed by singular value decomposition, two dominant characteristic vectors were found, one corresponding to a generic starvation response and another to a nutrient-specific starvation response that is similar in both organisms. Together these captured a remarkable 72% of the metabolite concentration changes in the full data set. The responses described by the generic starvation response vector (42%) included, for example, depletion of most biosynthetic intermediates. The nutrient-specific vector (30%) included key responses such as increased phosphoenolpyruvate signaling glucose deprivation and increased a-ketoglutarate signaling ammonia deprivation. Metabolic similarity across organisms extends from the covalent reaction network of metabolism to include many elements of metabolome response to nutrient deprivation as well.