Cellobiose Consumption Uncouples Extracellular Glucose Sensing and Glucose Metabolism in Saccharomyces cerevisiae.
Cellobiose Consumption Uncouples Extracellular Glucose Sensing and Glucose Metabolism in Saccharomyces cerevisiae.
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DOI：
10.1128/mbio.00855-17
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发表时间：
2017-08-08
期刊：
影响因子：
6.4
通讯作者：
Cate JHD
中科院分区：
文献类型：
--
作者：
Chomvong K;Benjamin DI;Nomura DK;Cate JHD
糖酵解是大多数生物体能量代谢的核心，并受到高度调节以实现最佳生长。在酿酒酵母中，通过糖酵解控制通量的反馈机制跨越了转录控制到细胞中的代谢物水平。使用纤维二糖消耗途径，我们将葡萄糖传感与碳利用解耦，揭示了诱导ATP消耗以驱动快速碳发酵的新的模块化控制层。磷酸果糖激酶-1（PFK 2）、H+-质膜ATP酶（PMA 1）和葡萄糖传感器（SNF 3和RGT 2）的β亚基的改变揭示了耦合细胞外葡萄糖传感以管理细胞中ATP水平的重要性。控制细胞ATP水平的上限可能是用于调节细胞中能量水平的一般机制，通过调节网络，可以在感知的饥饿条件下与ATP浓度解偶联。活细胞通过进化进行微调，以在其原生环境中茁壮成长。为特定生物技术应用创造生物体的基因组改变可能导致意外和不期望的表型。我们在酿酒酵母中使用最小合成生物系统作为平台，以揭示碳传感，饥饿条件和能量稳态之间的新联系。
Glycolysis is central to energy metabolism in most organisms and is highly regulated to enable optimal growth. In the yeast Saccharomyces cerevisiae, feedback mechanisms that control flux through glycolysis span transcriptional control to metabolite levels in the cell. Using a cellobiose consumption pathway, we decoupled glucose sensing from carbon utilization, revealing new modular layers of control that induce ATP consumption to drive rapid carbon fermentation. Alterations of the beta subunit of phosphofructokinase-1 (PFK2), H+-plasma membrane ATPase (PMA1), and glucose sensors (SNF3 and RGT2) revealed the importance of coupling extracellular glucose sensing to manage ATP levels in the cell. Controlling the upper bound of cellular ATP levels may be a general mechanism used to regulate energy levels in cells, via a regulatory network that can be uncoupled from ATP concentrations under perceived starvation conditions. Living cells are fine-tuned through evolution to thrive in their native environments. Genome alterations to create organisms for specific biotechnological applications may result in unexpected and undesired phenotypes. We used a minimal synthetic biological system in the yeast Saccharomyces cerevisiae as a platform to reveal novel connections between carbon sensing, starvation conditions, and energy homeostasis.