A global resource allocation strategy governs growth transition kinetics of Escherichia coli.
A global resource allocation strategy governs growth transition kinetics of Escherichia coli.
复制标题
DOI：
10.1038/nature24299
复制
发表时间：
2017-11-02
期刊：
影响因子：
64.8
通讯作者：
Hwa T
中科院分区：
文献类型：
--
作者：
Erickson DW;Schink SJ;Patsalo V;Williamson JR;Gerland U;Hwa T
系统生物学的一个重大挑战是从潜在的分子相互作用开始预测生命系统对扰动的动力学反应。长期以来，营养环境的变化一直被用来研究微生物的调节和适应现象，这是一个活跃的研究课题。尽管我们对分子间的相互作用了解甚多，这些相互作用控制着关键代谢过程对应用扰动的响应，但它们还不足以量化预测自下而上的建模。在这里，我们开发了一种自上而下的方法，将最近建立的粗粒度蛋白质组分配模型从稳态生长扩展到动力学状态。仅使用对潜在调节过程的定性知识和施加通量平衡条件，我们推导出细菌生长转变的定量模型，该模型独立于难以获得的动力学参数。由此产生的通量控制调节模型在没有可调参数的情况下，准确地预测了基因表达和生物量积累响应碳上升和下降（例如，双氧变化）的时间过程。正如模型预测和定量蛋白质组学验证的那样，由于蛋白质合成分配的严格策略，细胞在响应营养变化时表现出次优的恢复动力学，而这种策略并不是针对缓解特定的代谢瓶颈。我们的方法不依赖于动力学参数，因此指出了一个理论框架，用于描述广泛的此类动力学过程，而不需要详细了解潜在的生化反应。
A grand challenge of systems biology is to predict the kinetic responses of living systems to perturbations starting from the underlying molecular interactions. Changes in the nutrient environment have long been used to study regulation and adaptation phenomena in microorganisms and they remain a topic of active investigation. Although much is known about the molecular interactions that govern the regulation of key metabolic processes in response to applied perturbations, they are insufficiently quantified for predictive bottom-up modelling. Here we develop a top-down approach, expanding the recently established coarse-grained proteome allocation models from steady-state growth into the kinetic regime. Using only qualitative knowledge of the underlying regulatory processes and imposing the condition of flux balance, we derive a quantitative model of bacterial growth transitions that is independent of inaccessible kinetic parameters. The resulting flux-controlled regulation model accurately predicts the time course of gene expression and biomass accumulation in response to carbon upshifts and downshifts (for example, diauxic shifts) without adjustable parameters. As predicted by the model and validated by quantitative proteomics, cells exhibit suboptimal recovery kinetics in response to nutrient shifts owing to a rigid strategy of protein synthesis allocation, which is not directed towards alleviating specific metabolic bottlenecks. Our approach does not rely on kinetic parameters, and therefore points to a theoretical framework for describing a broad range of such kinetic processes without detailed knowledge of the underlying biochemical reactions.
登录
查看更多内容
影响因子：
9.9
作者：
Hermsen, Rutger;Okano, Hiroyuki;Hwa, Terence
通讯作者：
Hwa, Terence
影响因子：
3.4
作者：
Deutsch, Eric W.;Mendoza, Luis;Shteynberg, David;Farrah, Terry;Lam, Henry;Tasman, Natalie;Sun, Zhi;Nilsson, Erik;Pratt, Brian;Prazen, Bryan;Eng, Jimmy K.;Martin, Daniel B.;Nesvizhskii, Alexey I.;Aebersold, Ruedi
通讯作者：
Aebersold, Ruedi
影响因子：
48
作者：
Link, Hannes;Fuhrer, Tobias;Sauer, Uwe
通讯作者：
Sauer, Uwe
影响因子：
9.9
作者：
Kotte O;Volkmer B;Radzikowski JL;Heinemann M
通讯作者：
Heinemann M
影响因子：
5.6
作者：
DENNIS, PP;BREMER, H
通讯作者：
BREMER, H