Regulation of gene expression in flux balance models of metabolism
Regulation of gene expression in flux balance models of metabolism
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DOI：
10.1006/jtbi.2001.2405
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发表时间：
2001-11-07
影响因子：
2
通讯作者：
Palsson, B
中科院分区：
文献类型：
--
作者：
Covert, MW;Schilling, CH;Palsson, B
基因组规模的代谢网络，现在可以重建的基础上注释的基因组数据与生物体的生化和生理信息增强。可以进行数学分析来评估这些重建网络的能力。基于约束的框架，与通量平衡分析（FBA），已成功地用于预测的时间过程中的增长和副产物分泌，突变和敲除的影响，和基因表达谱。然而，FBA导致不正确的预测的情况下，监管效果是一个占主导地位的影响，生物体的行为。因此，需要在FBA中包括监管事件，以扩大其范围和预测能力。在这里，我们代表转录调控事件的能力，重建的代谢网络，以进一步限制可能的网络功能的空间的时间依赖性约束。使用一个简化的代谢/调节网络，生长在各种条件下进行模拟，以说明系统的影响，如分解代谢产物的阻遏，有氧/厌氧二次生长的转变和氨基酸生物合成途径的阻遏。在FBA中掺入转录调控事件使我们能够在系统水平上解释、分析和预测转录调控对细胞代谢的影响。(C)北京：科学出版社.
Genome-scale metabolic networks can now be reconstructed based on annotated genomic data augmented with biochemical and physiological information about the organism. Mathematical analysis can be performed to assess the capabilities of these reconstructed networks. The constraints-based framework, with flux balance analysis (FBA), has been used successfully to predict time course of growth and by-product secretion, effects of mutation and knock-outs, and gene expression profiles. However, FBA leads to incorrect predictions in situations where regulatory effects are a dominant influence on the behavior of the organism. Thus, there is a need to include regulatory events within FBA to broaden its scope and predictive capabilities. Here we represent transcriptional regulatory events as time-dependent constraints on the capabilities of a reconstructed metabolic network to further constrain the space of possible network functions. Using a simplified metabolic/regulatory network, growth is simulated under various conditions to illustrate systemic effects such as catabolite repression, the aerobic/anaerobic diauxic shift and amino acid biosynthesis pathway repression. The incorporation of transcriptional regulatory events in FBA enables us to interpret, analyse and predict the effects of transcriptional regulation on cellular metabolism at the systemic level. (C) 2001 Academic Press.