Overflow metabolism in Escherichia coli results from efficient proteome allocation.
Overflow metabolism in Escherichia coli results from efficient proteome allocation.
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DOI：
10.1038/nature15765
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发表时间：
2015-12-03
期刊：
影响因子：
64.8
通讯作者：
Hwa T
中科院分区：
文献类型：
--
作者：
Basan M;Hui S;Okano H;Zhang Z;Shen Y;Williamson JR;Hwa T
溢出新陈代谢指的是看似浪费的策略，在这种策略中，细胞使用发酵而不是更有效的呼吸来产生能量，尽管有氧气可用。在癌症生长的背景下，这种现象被称为华宝效应，这种现象在快速生长的细胞中普遍存在，包括细菌、真菌和哺乳动物细胞，但尽管进行了数十年的研究，它的起源仍然是个谜。在这里，我们研究了大肠杆菌中的代谢溢出，表明它是一种全球性的生理反应，用于应对不同生长条件下不断变化的蛋白质组对能量、生物发生和生物量合成的需求。一个简单的蛋白质组资源分配模型可以定量地解释所有观察到的行为，并准确地预测对新扰动的反应。该模型的关键假设是，呼吸生成能量的蛋白质组成本高于发酵生成的蛋白质组成本，并通过定量质谱学直接测量蛋白质丰度进行了定量验证。
Overflow metabolism refers to the seemingly wasteful strategy in which cells use fermentation instead of the more efficient respiration to generate energy, despite the availability of oxygen. Known as Warburg effect in the context of cancer growth, this phenomenon occurs ubiquitously for fast growing cells, including bacteria, fungi, and mammalian cells, but its origin has remained mysterious despite decades of research. Here we study metabolic overflow in E. coli and show that it is a global physiological response used to cope with changing proteomic demands of energy biogenesis and biomass synthesis under different growth conditions. A simple model of proteomic resource allocation can quantitatively account for all of the observed behaviors and accurately predict responses to novel perturbations. The key hypothesis of the model, that the proteome cost of energy biogenesis by respiration exceeds that by fermentation, is quantitatively confirmed by direct measurement of protein abundances via quantitative mass spectrometry.