(Im)Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis.
(Im)Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis.
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DOI：
10.1186/1752-0509-7-131
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发表时间：
2013-11-21
影响因子：
--
通讯作者：
Westerhoff HV
中科院分区：
文献类型：
--
作者：
He F;Fromion V;Westerhoff HV
代谢控制分析（MCA）和供需理论导致了对代谢网络系统特性的可观理解，代谢网络只受代谢调节。供需理论尚未明确考虑基因表达调控，而MCA的一种变体，即层次控制分析（HCA）已经这样做了。现有的基于控制工程方法的分析并没有非常明确是否涉及代谢或基因表达调节，而是设计了不同的调节方式，这些方式可以组织调节，并有可能使适应变得完美。本研究将控制工程与经典MCA结合，辅以供需理论与HCA。由于基因表达调控涉及时间整合，它被确定为控制工程中已知的“积分控制”（或接近积分控制）的自然实例。然后，本研究侧重于对网络中过程活动扰动的鲁棒性和适应性，这些扰动可能由环境扰动、突变或慢噪声引起。然而，研究表明，这种“整体控制”很少会导致“完美适应”：尽管基因表达调节增加了重要代谢物浓度的稳健性，但很少会使它们无限稳健性。为了实现完美的适应，蛋白质的降解反应在蛋白质浓度上应该是零级的，这对于稳定生长的细胞来说可能是罕见的。一个整合控制工程、代谢和层次控制分析方法的新框架，提高了对代谢和基因表达调节的生物系统的理解。特别是，新方法使人们能够解决已经和正在被基因组学和系统生物学识别的细胞内生化网络是否符合控制工程设计的“完美”调节结构，例如-à-vis鲁棒性等最佳功能。在某种程度上，它们不是，分析表明它们如何可能成为这样，这反过来应该促进合成生物学和代谢工程。
Metabolic control analysis (MCA) and supply–demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply–demand theory has not yet considered gene-expression regulation explicitly whilst a variant of MCA, i.e. Hierarchical Control Analysis (HCA), has done so. Existing analyses based on control engineering approaches have not been very explicit about whether metabolic or gene-expression regulation would be involved, but designed different ways in which regulation could be organized, with the potential of causing adaptation to be perfect. This study integrates control engineering and classical MCA augmented with supply–demand theory and HCA. Because gene-expression regulation involves time integration, it is identified as a natural instantiation of the ‘integral control’ (or near integral control) known in control engineering. This study then focuses on robustness against and adaptation to perturbations of process activities in the network, which could result from environmental perturbations, mutations or slow noise. It is shown however that this type of ‘integral control’ should rarely be expected to lead to the ‘perfect adaptation’: although the gene-expression regulation increases the robustness of important metabolite concentrations, it rarely makes them infinitely robust. For perfect adaptation to occur, the protein degradation reactions should be zero order in the concentration of the protein, which may be rare biologically for cells growing steadily. A proposed new framework integrating the methodologies of control engineering and metabolic and hierarchical control analysis, improves the understanding of biological systems that are regulated both metabolically and by gene expression. In particular, the new approach enables one to address the issue whether the intracellular biochemical networks that have been and are being identified by genomics and systems biology, correspond to the ‘perfect’ regulatory structures designed by control engineering vis-à-vis optimal functions such as robustness. To the extent that they are not, the analyses suggest how they may become so and this in turn should facilitate synthetic biology and metabolic engineering.
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DOI：
10.1038/nrmicro1949
发表时间：
2009-02
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
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影响因子：
5.4
作者：
Quinton-Tulloch, Mark J.;Bruggeman, Frank J.;Westerhoff, Hans V.
通讯作者：
Westerhoff, Hans V.
在单细胞分辨率下监测的大肠杆菌培养物中的细胞分裂。
影响因子：
4.2
作者：
Roostalu, Johanna;Joers, Arvi;Luidalepp, Hannes;Kaldalu, Niilo;Tenson, Tanel
通讯作者：
Tenson, Tanel
影响因子：
64.5
作者：
Muzzey D;Gómez-Uribe CA;Mettetal JT;van Oudenaarden A
通讯作者：
van Oudenaarden A
影响因子：
9.8
作者：
Chin CS;Chubukov V;Jolly ER;DeRisi J;Li H
通讯作者：
Li H