Stoichiometric modeling of Clostridium acetobutylicum fermentations with non-linear constraints
Stoichiometric modeling of Clostridium acetobutylicum fermentations with non-linear constraints
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DOI：
10.1016/s0168-1656(99)00022-x
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发表时间：
1999-05-28
影响因子：
4.1
通讯作者：
Papoutsakis, ET
中科院分区：
文献类型：
--
作者：
Desai, RP;Nielsen, LK;Papoutsakis, ET
乙酰丁酸梭菌及其相关菌株的化学计量模型已被推导出来。该模型的化学计量矩阵包含一个奇异点，这使得无法计算一组描述主要代谢活动的唯一通量。为了解决奇点，我们开发了一个非线性约束有关醋酸和丁酸摄取通量。随后，我们开发了一个软件包，利用模型无关的启发式全局优化方法来解决由此产生的非线性问题。我们通过将计算的丁酸酯生产途径通量曲线与测量的细胞内pH曲线相关联，验证了非线性约束的使用。最后，我们研究了一个受控的批量发酵，以确定酸的形成途径在溶剂生成过程中起关键作用。讨论了将化学计量模型重新表述为约束最小化问题的更广泛用途。(C) 1999 Elsevier Science B.V.版权所有
A stoichiometric model of Clostridium acetobutylicum and related strains has been previously derived. The stoichiometric matrix of the model contains a singularity which has prevented the calculation of a unique set of fluxes which describe the primary metabolic activity. To resolve the singularity, we have developed a non-linear constraint relating the acetate and butyrate uptake fluxes. Subsequently, we developed a software package utilizing a model independent heuristic global optimization approach to solve the resultant non-linear problem. We have validated the use of the non-linear constraint by correlating calculated butyrate production pathway flux profiles with measured intracellular pH profiles. Finally, we examined a controled batch fermentation to determine that the acid formation pathways play critical roles throughout solventogenesis. The broader usefulness of reformulating the stoichiometric model as a constrained minimization problem is discussed. (C) 1999 Elsevier Science B.V. All rights reserved.