An expanded whole-cell model of E. coli links cellular physiology with mechanisms of growth rate control.
An expanded whole-cell model of E. coli links cellular physiology with mechanisms of growth rate control.
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DOI：
10.1038/s41540-022-00242-9
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发表时间：
2022-08-19
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
生长和环境反应对于生物体生存和适应不断变化的环境至关重要。为了模拟新的条件和捕捉动态响应的环境变化在一个发展中的全细胞模型的E。大肠杆菌中，我们纳入了额外的调控，包括动态的全局调节鸟苷四磷酸（ppGpp），随着沿着动态的氨基酸生物合成和翻译。与该模型，我们表明，在扰动ppGpp条件下，小分子反馈抑制途径，除了调节表达，发挥作用，在ppGpp调节生长。我们还发现，氨基酸合成途径失调的模拟提供了与实验结果相当的平均氨基酸浓度预测，但在单细胞水平上，浓度意外地显示出规律性的波动。此外，在营养物质可用性的上移和下移期间，模拟细胞的响应类似于mRNA：rRNA比率的瞬时增加。这种额外的模拟功能应该支持各种新的应用和E.大肠杆菌全细胞建模项目。
Growth and environmental responses are essential for living organisms to survive and adapt to constantly changing environments. In order to simulate new conditions and capture dynamic responses to environmental shifts in a developing whole-cell model of E. coli, we incorporated additional regulation, including dynamics of the global regulator guanosine tetraphosphate (ppGpp), along with dynamics of amino acid biosynthesis and translation. With the model, we show that under perturbed ppGpp conditions, small molecule feedback inhibition pathways, in addition to regulation of expression, play a role in ppGpp regulation of growth. We also found that simulations with dysregulated amino acid synthesis pathways provide average amino acid concentration predictions that are comparable to experimental results but on the single-cell level, concentrations unexpectedly show regular fluctuations. Additionally, during both an upshift and downshift in nutrient availability, the simulated cell responds similarly with a transient increase in the mRNA:rRNA ratio. This additional simulation functionality should support a variety of new applications and expansions of the E. coli Whole-Cell Modeling Project.
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影响因子：
28.3
作者：
Li SH;Li Z;Park JO;King CG;Rabinowitz JD;Wingreen NS;Gitai Z
通讯作者：
Gitai Z
影响因子：
64.8
作者：
Erickson DW;Schink SJ;Patsalo V;Williamson JR;Gerland U;Hwa T
通讯作者：
Hwa T
DOI：
10.1073/pnas.1320396110
发表时间：
2014-01-07
影响因子：
11.1
作者：
Feng, Jingchen;Kessler, David A.;Levine, Herbert
通讯作者：
Levine, Herbert
影响因子：
--
作者：
Liebeke, Manuel;Doerries, Kirsten;Lalk, Michael
通讯作者：
Lalk, Michael
DOI：
10.1073/pnas.2136632100
发表时间：
2003-12-23
影响因子：
11.1
作者：
Liao, JC;Boscolo, R;Roychowdhury, VP
通讯作者：
Roychowdhury, VP