Reprogramming of Escherichia coli K-12 metabolism during the initial phase of transition from an anaerobic to a micro-aerobic environment.

Reprogramming of Escherichia coli K-12 metabolism during the initial phase of transition from an anaerobic to a micro-aerobic environment.
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DOI:
10.1371/journal.pone.0025501
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Green J
Green J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Trotter EW;Rolfe MD;Hounslow AM;Craven CJ;Williamson MP;Sanguinetti G;Poole RK;Green J

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许多细菌在具有不同氧气可利用性的环境之间进行转换,这是它们自然生活方式的一部分,也是在生物技术过程中的一部分。然而,当细菌经历氧气供应变化时的适应动力学还没有得到充分的研究。模式菌兼兼性厌氧菌大肠杆菌K-12为探索这一过程提供了一个理想的系统。大肠杆菌K-12在从厌氧条件向微好氧条件转变的初始阶段的时间分辨转录谱显示,基因表达的重新编程与从发酵代谢向呼吸代谢的转换一致。转录丰度的变化与选定的中央代谢蛋白丰度的变化相匹配。概率状态空间模型被用来推断两个关键调控因子FNR(O2传感)和PdhR(丙酮酸传感)的活性。该模型表明,在从厌氧环境向微好氧环境的转变过程中,这两种调控因子都被迅速失活。外部代谢组和蛋白质水平的分析表明,在适应过程中,培养物经历了不同的生理状态,特征是丙酮酸甲酸裂解酶(PFL)迅速失活,丙酮酸脱氢酶复合体(PDHC)活性诱导较慢,丙酮酸短暂排泄,与预测的PdhR和FNR失活一致。通过引入有限的氧气供应,结合时间分辨的转录本、蛋白质和代谢物图谱,以及概率建模,以及概率建模,揭示了丙酮酸(由PdhR感应)是协调大肠杆菌K-12基因表达重新编程的关键代谢信号,在从厌氧向微好氧条件转变的过程中与O2传感器FNR一起工作。
Many bacteria undergo transitions between environments with differing O2 availabilities as part of their natural lifestyles and during biotechnological processes. However, the dynamics of adaptation when bacteria experience changes in O2 availability are understudied. The model bacterium and facultative anaerobe Escherichia coli K-12 provides an ideal system for exploring this process. Time-resolved transcript profiles of E. coli K-12 during the initial phase of transition from anaerobic to micro-aerobic conditions revealed a reprogramming of gene expression consistent with a switch from fermentative to respiratory metabolism. The changes in transcript abundance were matched by changes in the abundances of selected central metabolic proteins. A probabilistic state space model was used to infer the activities of two key regulators, FNR (O2 sensing) and PdhR (pyruvate sensing). The model implied that both regulators were rapidly inactivated during the transition from an anaerobic to a micro-aerobic environment. Analysis of the external metabolome and protein levels suggested that the cultures transit through different physiological states during the process of adaptation, characterized by the rapid inactivation of pyruvate formate-lyase (PFL), a slower induction of pyruvate dehydrogenase complex (PDHC) activity and transient excretion of pyruvate, consistent with the predicted inactivation of PdhR and FNR. Perturbation of anaerobic steady-state cultures by introduction of a limited supply of O2 combined with time-resolved transcript, protein and metabolite profiling, and probabilistic modeling has revealed that pyruvate (sensed by PdhR) is a key metabolic signal in coordinating the reprogramming of E. coli K-12 gene expression by working alongside the O2 sensor FNR during transition from anaerobic to micro-aerobic conditions.
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