Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism.
Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism.
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基本通量模式分析揭示环化途径是中心碳代谢 NADPH 再生的有力途径
DOI：
10.1371/journal.pone.0129837
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Xie X
中科院分区：
文献类型：
--
作者：
Rui B;Yi Y;Shen T;Zheng M;Zhou W;Du H;Fan Y;Wang Y;Zhang Z;Xu S;Liu Z;Wen H;Xie X
NADPH的再生能力因其在抵抗氧化应激中的重要作用而受到越来越多的研究关注。此外，NADPH的可用性一直被认为是生产具有工业价值的化合物的限制因素。中心碳代谢携带碳骨架通量，支持NADPH再生酶的运行，并提供灵活性，以应对不同细胞内环境的NADPH需求。为了深入了解其NADPH再生能力，采用基模方法计算了一个代表中心碳代谢的网络的所有基元通量模式。基于这些模式的代谢通量分布，采用自组织MAP聚类算法对NADPH再生率较高的EFM进行了聚类分析。利用聚类结果研究了总NADPH再生通量与各NADPH产生酶通量之间的关系。通过热力学分析，确定了支持高NADPH再生的几种反应组合，这些反应组合在细胞中是可行的，并与大量的实验报道相吻合。同时，这些反应组合呈现出一些共同的特征：在产生NADPH的组合中存在一个或两个脱羧基氧化反应，组合的组成包括一定的糖异生途径。这些发现表明，环化途径是提高细菌中心碳代谢NADPH再生能力的有效途径。
NADPH regeneration capacity is attracting growing research attention due to its important role in resisting oxidative stress. Besides, NADPH availability has been regarded as a limiting factor in production of industrially valuable compounds. The central carbon metabolism carries the carbon skeleton flux supporting the operation of NADPH-regenerating enzyme and offers flexibility in coping with NADPH demand for varied intracellular environment. To acquire an insightful understanding of its NADPH regeneration capacity, the elementary mode method was employed to compute all elementary flux modes (EFMs) of a network representative of central carbon metabolism. Based on the metabolic flux distributions of these modes, a cluster analysis of EFMs with high NADPH regeneration rate was conducted using the self-organizing map clustering algorithm. The clustering results were used to study the relationship between the flux of total NADPH regeneration and the flux in each NADPH producing enzyme. The results identified several reaction combinations supporting high NADPH regeneration, which are proven to be feasible in cells via thermodynamic analysis and coincident with a great deal of previous experimental report. Meanwhile, the reaction combinations showed some common characteristics: there were one or two decarboxylation oxidation reactions in the combinations that produced NADPH and the combination constitution included certain gluconeogenesis pathways. These findings suggested cyclization pathways as a powerful way for NADPH regeneration capacity of bacterial central carbon metabolism.
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影响因子：
14.9
作者：
Chang A;Scheer M;Grote A;Schomburg I;Schomburg D
通讯作者：
Schomburg D
影响因子：
3.4
作者：
Jankowski, Matthew D.;Henry, Christopher S.;Hatzimanikatis, Vassily
通讯作者：
Hatzimanikatis, Vassily
DOI：
10.1038/nrmicro3032
发表时间：
2013-07
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
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影响因子：
3.8
作者：
Chassagnole, C;Noisommit-Rizzi, N;Reuss, M
通讯作者：
Reuss, M
影响因子：
9.9
作者：
通讯作者：
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