A systems biology approach to investigate the effect of pH-induced gene regulation on solvent production by Clostridium acetobutylicum in continuous culture.
A systems biology approach to investigate the effect of pH-induced gene regulation on solvent production by Clostridium acetobutylicum in continuous culture.
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DOI：
10.1186/1752-0509-5-10
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发表时间：
2011-01-19
影响因子：
--
通讯作者：
Wolkenhauer O
中科院分区：
文献类型：
--
作者：
Haus S;Jabbari S;Millat T;Janssen H;Fischer RJ;Bahl H;King JR;Wolkenhauer O
乙酰丁酸梭菌是一种厌氧细菌，以其溶剂生产能力而闻名，即关于散装化学品丙酮和丁醇，后者是一种高效的生物燃料。为了优化C. acetobutylicum的丁醇产量，并在工业规模上进行开发，必须尽可能充分地了解ph诱导的基因调控对C. acetobutylicum连续培养中溶剂产量的影响。我们提出了一个常微分方程模型，结合代谢网络控制溶剂生产和调节在遗传水平的酶需要这一过程。用连续培养的实验数据参数化模型，我们证明了pH对发酵产物的影响：在高pH （pH 5.7）下，酸是主要产物，而在低pH （pH 4.5）下，它转向溶剂。通过对模型的稳态分析，我们重点研究了在连续培养发酵中如何利用C. acetobutylicum基因表达的改变来提高丁醇产量。将基因调控纳入C. acetobutylicum的溶剂生产模型中，可以准确地表示ph诱导的溶剂生产转换，并对可能的合成生物学方法进行理论研究。稳态分析表明，要提高丁醇产量，改变单一溶剂相关基因的表达是不够的；需要一种针对两个或更多基因的更复杂的方法。
Clostridium acetobutylicum is an anaerobic bacterium which is known for its solvent-producing capabilities, namely regarding the bulk chemicals acetone and butanol, the latter being a highly efficient biofuel. For butanol production by C. acetobutylicum to be optimized and exploited on an industrial scale, the effect of pH-induced gene regulation on solvent production by C. acetobutylicum in continuous culture must be understood as fully as possible. We present an ordinary differential equation model combining the metabolic network governing solvent production with regulation at the genetic level of the enzymes required for this process. Parameterizing the model with experimental data from continuous culture, we demonstrate the influence of pH upon fermentation products: at high pH (pH 5.7) acids are the dominant product while at low pH (pH 4.5) this switches to solvents. Through steady-state analyses of the model we focus our investigations on how alteration in gene expression of C. acetobutylicum could be exploited to increase butanol yield in a continuous culture fermentation. Incorporating gene regulation into the model of solvent production by C. acetobutylicum enables an accurate representation of the pH-induced switch to solvent production to be obtained and theoretical investigations of possible synthetic-biology approaches to be pursued. Steady-state analyses suggest that, to increase butanol yield, alterations in the expression of single solvent-associated genes are insufficient; a more complex approach targeting two or more genes is required.
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影响因子：
4.3
作者：
Millat, Thomas;Bullinger, Eric;Wolkenhauer, Olaf
通讯作者：
Wolkenhauer, Olaf
DOI：
10.1007/bf00499955
发表时间：
1982-01-01
期刊：
EUROPEAN JOURNAL OF APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
影响因子：
--
作者：
BAHL, H;ANDERSCH, W;GOTTSCHALK, G
通讯作者：
GOTTSCHALK, G
影响因子：
3.2
作者：
Fiedler, Tomas;Mix, Maren;Fischer, Ralf-Joerg
通讯作者：
Fischer, Ralf-Joerg
影响因子：
8.4
作者：
Desai, Ruchir P.;Harris, Latonia M.;Papoutsakis, Eleftherios T.
通讯作者：
Papoutsakis, Eleftherios T.
影响因子：
3.2
作者：
FISCHER, RJ;HELMS, J;DURRE, P
通讯作者：
DURRE, P