pH-induced gene regulation of solvent production by Clostridium acetobutylicum in continuous culture: parameter estimation and sporulation modelling.
pH-induced gene regulation of solvent production by Clostridium acetobutylicum in continuous culture: parameter estimation and sporulation modelling.
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DOI：
10.1016/j.mbs.2012.11.004
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发表时间：
2013-02
影响因子：
4.3
通讯作者：
Jabbari S
中科院分区：
文献类型：
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作者：
Thorn GJ;King JR;Jabbari S
从数据来看，先前推导的代谢ODE系统是欠定的。在实验中加入pH值变化后的孢子部分可提高拟合度。假设大约75%的培养孢子进一步提高了拟合。乙酰辅酶A、丁酰辅酶A和孢子的分析将验证模型。在厌氧内孢子形成革兰氏阳性细菌丙酮丁醇梭菌中的丙酮-丁醇（AB）发酵方法可用作生物燃料，特别是丁醇的生产者。最近的工作集中在试图提高发酵方法的效率，通过改变环境条件或通过修饰基因组以选择性地有利于一种特定溶剂的生产。利用C.丙酮丁醇发生在两个阶段：最初产生和排泄乙酸和丁酸，然后随着外部pH福尔斯下降，乙酸和丁酸被摄入并进一步代谢成溶剂丙酮、丁醇和乙醇。为了优化丁醇生产，了解pH值如何影响代谢过程中的酶控制反应非常重要。我们调整了代谢网络的常微分方程模型，在遗传水平上调节所需的酶;使用连续培养产生的实验数据对模型进行参数化，我们改进了以前的点预测（S。豪斯，S. Jabbari，T.米拉特詹森河J. Fisher，H.巴尔King，O. Wolkenhauer，A systems biology approach to investigate the effect of pH-induced gene regulation on solvent production by Clostridium acetobutylicum in continuous culture，BMC Systems Biology 5（2011）），通过使用不同的优化方法并通过计算置信区间和相关系数。我们发现，特别是参数是病态的数据，两个独立的集群的参数出现相关，反映了两个代谢中间体的重要性。我们进一步扩展模型，包括梭菌的生存机制，孢子形成的另一个方面，并通过计算赤池信息标准值发现，有一些证据的存在孢子形成的转变。
► Metabolic ODE system as previously derived is underdetermined from the data. ► Inclusion of spore fraction post-pH shift in experiments improves the fit. ► Assuming approximately 75% of culture sporulates further improves the fit. ► Assays of acetyl-CoA, butyryl-CoA and spores will validate model. The acetone–butanol (AB) fermentation process in the anaerobic endospore-forming Gram-positive bacterium Clostridium acetobutylicum is useful as a producer of biofuels, particularly butanol. Recent work has concentrated on trying to improve the efficiency of the fermentation method, either through changes in the environmental conditions or by modifying the genome to selectively favour the production of one particular solvent over others. Fermentation of glucose by C. acetobutylicum occurs in two stages: initially the acids acetate and butyrate are produced and excreted and then, as the external pH falls, acetate and butyrate are ingested and further metabolised into the solvents acetone, butanol and ethanol. In order to optimise butanol production, it is important to understand how pH affects the enzyme-controlled reactions in the metabolism process. We adapt an ordinary differential equation model of the metabolic network with regulation at the genetic level for the required enzymes; parametrising the model using experimental data generated from continuous culture, we improve on previous point predictions (S. Haus, S. Jabbari, T. Millat, H. Janssen, R.-J. Fisher, H. Bahl, J. R. King, O. Wolkenhauer, A systems biology approach to investigate the effect of pH-induced gene regulation on solvent production by Clostridium acetobutylicum in continuous culture, BMC Systems Biology 5 (2011)) both by using a different optimisation approach and by computing confidence intervals and correlation coefficients. We find in particular that the parameters are ill-determined from the data and that two separate clusters of parameters appear correlated, reflecting the importance of two metabolic intermediates. We extend the model further to include another aspect of the clostridial survival mechanism, sporulation, and by computation of the Akaike Information Criterion values find that the there is some evidence for the presence of sporulation during the shift.
DOI：
10.1093/bioinformatics/btp619
发表时间：
2010-01-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Toni T;Stumpf MP
通讯作者：
Stumpf MP
影响因子：
--
作者：
Ashyraliyev, Maksat;Jaeger, Johannes;Blom, Joke G.
通讯作者：
Blom, Joke G.
影响因子：
--
作者：
Haus S;Jabbari S;Millat T;Janssen H;Fischer RJ;Bahl H;King JR;Wolkenhauer O
通讯作者：
Wolkenhauer O