Metabolic flux ratio analysis and multi-objective optimization revealed a globally conserved and coordinated metabolic response of E. coli to paraquat-induced oxidative stress.
Metabolic flux ratio analysis and multi-objective optimization revealed a globally conserved and coordinated metabolic response of E. coli to paraquat-induced oxidative stress.
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DOI：
10.1039/c2mb25285f
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发表时间：
2013-01
影响因子：
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通讯作者：
Tie Shen;B. Rui;Hong Zhou;Ximin Zhang;Yin Yi;H. Wen;Hao-ran Zheng;Jihui Wu;Yunyu Shi
中科院分区：
文献类型：
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作者：
Tie Shen;B. Rui;Hong Zhou;Ximin Zhang;Yin Yi;H. Wen;Hao-ran Zheng;Jihui Wu;Yunyu Shi
微生物适应环境变化的能力，如营养或氧气的可用性，对其竞争适应性和生存至关重要。因此，细胞目标和对极端环境的代谢反应的策略引起了极大的兴趣，因此越来越多地被探索。然而，细胞目标的复杂的调控结构的代谢变化尚未完全阐明和更多的细节有关的定量行为的代谢通量再分配需要了解系统范围内的生物学意义的这种反应。在这项研究中，参与中心碳代谢的细胞内代谢通量比通过分数（13）C-标记和代谢通量比分析（MetaFoR）的野生型E.大肠杆菌菌株JM 101在恒化器中的氧化环境中。我们观察到通过磷酸烯醇式丙酮酸羧化酶（PEPCK），磷酸烯醇式丙酮酸羧化酶（PEPC），苹果酸酶（MEZ）和丝氨酸羟甲基转移酶（SHMT）的流量显着增加。本文采用基于ε-约束的多目标优化方法，以大肠杆菌iJR 904基因组规模的电子模拟模型为基础，研究了生物量产量和还原力之间的权衡关系。coli K-12。理论上的代谢再分配支持转氢酶途径在E. coli抗氧化应激的能力。测量的比率和理论的再分配之间的协议建立了NADPH合成的重要性作为目标的代谢重编程，发生在响应氧化应激。我们的工作提出了一个框架，结合代谢通量比分析和多目标优化，以调查在不同的环境条件下发生的代谢权衡。我们的研究结果导致了E.大肠杆菌对百草枯诱导的氧化应激反应是全局保守和协调的。
The ability of a microorganism to adapt to changes in the environment, such as in nutrient or oxygen availability, is essential for its competitive fitness and survival. The cellular objective and the strategy of the metabolic response to an extreme environment are therefore of tremendous interest and, thus, have been increasingly explored. However, the cellular objective of the complex regulatory structure of the metabolic changes has not yet been fully elucidated and more details regarding the quantitative behaviour of the metabolic flux redistribution are required to understand the systems-wide biological significance of this response. In this study, the intracellular metabolic flux ratios involved in the central carbon metabolism were determined by fractional (13)C-labeling and metabolic flux ratio analysis (MetaFoR) of the wild-type E. coli strain JM101 at an oxidative environment in a chemostat. We observed a significant increase in the flux through phosphoenolpyruvate carboxykinase (PEPCK), phosphoenolpyruvate carboxylase (PEPC), malic enzyme (MEZ) and serine hydroxymethyltransferase (SHMT). We applied an ε-constraint based multi-objective optimization to investigate the trade-off relationships between the biomass yield and the generation of reductive power using the in silico iJR904 genome-scale model of E. coli K-12. The theoretical metabolic redistribution supports that the trans-hydrogenase pathway should not play a direct role in the defence mounted by E. coli against oxidative stress. The agreement between the measured ratio and the theoretical redistribution established the significance of NADPH synthesis as the goal of the metabolic reprogramming that occurs in response to oxidative stress. Our work presents a framework that combines metabolic flux ratio analysis and multi-objective optimization to investigate the metabolic trade-offs that occur under varied environmental conditions. Our results led to the proposal that the metabolic response of E. coli to paraquat-induced oxidative stress is globally conserved and coordinated.