Transcriptional regulation is insufficient to explain substrate-induced flux changes in Bacillus subtilis.
Transcriptional regulation is insufficient to explain substrate-induced flux changes in Bacillus subtilis.
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DOI：
10.1038/msb.2013.66
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发表时间：
2013-11-26
影响因子：
9.9
通讯作者：
Sauer, Uwe
中科院分区：
文献类型：
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作者：
Chubukov, Victor;Uhr, Markus;Le Chat, Ludovic;Kleijn, Roelco J.;Jules, Matthieu;Link, Hannes;Aymerich, Stephane;Stelling, Joerg;Sauer, Uwe
微生物被认为调节其代谢的关键方式之一是通过转录调节来调节酶的可用性。然而，有限的成功的努力来操纵代谢通量通过重新布线的转录网络的想法，即转录丰度控制代谢通量投下了怀疑。在这项研究中，我们调查控制代谢通量的模式细菌枯草芽孢杆菌的量化通量，成绩单，和代谢产物在8个代谢状态下，不同的环境条件下执行。我们发现，大多数酶的通量开关之间的状态，如参与底物摄取，表现出大的相应的转录变化。然而，对于大多数的酶在中央代谢，酶浓度不足以解释所观察到的流量只有一些反应中的三羧酸循环酶的变化近似成比例的流量变化。令人惊讶的是，底物的变化所揭示的代谢组学也不足以解释所观察到的通量，留下了很大的作用，变构调节和酶修饰的代谢通量的控制。
One of the key ways in which microbes are thought to regulate their metabolism is by modulating the availability of enzymes through transcriptional regulation. However, the limited success of efforts to manipulate metabolic fluxes by rewiring the transcriptional network has cast doubt on the idea that transcript abundance controls metabolic fluxes. In this study, we investigate control of metabolic flux in the model bacterium Bacillus subtilis by quantifying fluxes, transcripts, and metabolites in eight metabolic states enforced by different environmental conditions. We find that most enzymes whose flux switches between on and off states, such as those involved in substrate uptake, exhibit large corresponding transcriptional changes. However, for the majority of enzymes in central metabolism, enzyme concentrations were insufficient to explain the observed fluxes—only for a number of reactions in the tricarboxylic acid cycle were enzyme changes approximately proportional to flux changes. Surprisingly, substrate changes revealed by metabolomics were also insufficient to explain observed fluxes, leaving a large role for allosteric regulation and enzyme modification in the control of metabolic fluxes.
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影响因子：
4.3
作者：
Goyal, Sidhartha;Yuan, Jie;Wingreen, Ned S.
通讯作者：
Wingreen, Ned S.
DOI：
10.1073/pnas.1114235109
发表时间：
2012-03-27
影响因子：
11.1
作者：
Chubukov, Victor;Zuleta, Ignacio A.;Li, Hao
通讯作者：
Li, Hao
影响因子：
7.4
作者：
Fuhrer, Tobias;Heer, Dominik;Zamboni, Nicola
通讯作者：
Zamboni, Nicola
影响因子：
6.7
作者：
Beste DJ;Bonde B;Hawkins N;Ward JL;Beale MH;Noack S;Nöh K;Kruger NJ;Ratcliffe RG;McFadden J
通讯作者：
McFadden J
影响因子：
9.9
作者：
通讯作者：
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