A genome-scale computational study of the interplay between transcriptional regulation and metabolism.

A genome-scale computational study of the interplay between transcriptional regulation and metabolism.
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DOI:
10.1038/msb4100141
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发表时间:
2007
影响因子:
9.9
通讯作者:
Ruppin, Eytan
Ruppin, Eytan
中科院分区:
生物学1区
文献类型:
--
作者:
Shlomi, Tomer;Eisenberg, Yariv;Sharan, Roded;Ruppin, Eytan

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本文提出了一种新的方法,稳态调节通量平衡分析(SR-FBA),预测基因表达和代谢通量的大规模集成代谢调控模型。使用SR-FBA来研究大肠杆菌的代谢,我们量化了不同水平的代谢和转录调控约束决定代谢行为的程度:代谢约束决定了45-51%的代谢基因的通量活性状态,这取决于生长培养基,而转录调控决定了13-20%的基因的通量活性状态。相当数量的36个基因是冗余表达的,也就是说,即使它们的相关反应的通量为零,它们也被表达,这表明它们没有针对细胞通量需求进行最佳调节。其余约30%的基因的未确定状态表明它们可能代表给定生长培养基内的代谢变异性。总的来说,SR-FBA使人们能够解决许多关于调节和代谢之间相互作用的新问题。
This paper presents a new method, steady-state regulatory flux balance analysis (SR-FBA), for predicting gene expression and metabolic fluxes in a large-scale integrated metabolic–regulatory model. Using SR-FBA to study the metabolism of Escherichia coli, we quantify the extent to which the different levels of metabolic and transcriptional regulatory constraints determine metabolic behavior: metabolic constraints determine the flux activity state of 45–51% of metabolic genes, depending on the growth media, whereas transcription regulation determines the flux activity state of 13–20% of the genes. A considerable number of 36 genes are redundantly expressed, that is, they are expressed even though the fluxes of their associated reactions are zero, indicating that they are not optimally tuned for cellular flux demands. The undetermined state of the remaining ∼30% of the genes suggests that they may represent metabolic variability within a given growth medium. Overall, SR-FBA enables one to address a host of new questions concerning the interplay between regulation and metabolism.
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