Department of Systems Biology & Bioinformatics, Institute of Computer Science, University of Rostock, University of Rostock, Ulmenstr. 69, 18051, Rostock, Germany.
Microb Biotechnol. 2013 Sep;6(5):526-39. doi: 10.1111/1751-7915.12033. Epub 2013 Jan 21.
In a continuous culture under phosphate limitation the metabolism of Clostridium acetobutylicum depends on the external pH level. By comparing seven steady-state conditions between pH 5.7 and pH 4.5 we show that the switch from acidogenesis to solventogenesis occurs between pH 5.3 and pH 5.0 with an intermediate state at pH 5.1. Here, an integrative study is presented investigating how a changing external pH level affects the clostridial acetone-butanol-ethanol (ABE) fermentation pathway. This is of particular interest as the biotechnological production of n-butanol as biofuel has recently returned into the focus of industrial applications. One prerequisite is the furthering of the knowledge of the factors determining the solvent production and their integrative regulations. We have mathematically analysed the influence of pH-dependent specific enzyme activities of branch points of the metabolism on the product formation. This kinetic regulation was compared with transcriptomic regulation regarding gene transcription and the proteomic profile. Furthermore, both regulatory mechanisms were combined yielding a detailed projection of their individual and joint effects on the product formation. The resulting model represents an important platform for future developments of industrial butanol production based on C. acetobutylicum.
在磷酸盐限制的连续培养中，丙酮丁醇梭菌的代谢依赖于外部 pH 值。通过比较 pH 值 5.7 和 pH 值 4.5 之间的七种稳态条件，我们表明从产酸到溶剂生成的转变发生在 pH 值 5.3 和 pH 值 5.0 之间，pH 值 5.1 为中间状态。在这里，我们提出了一项综合研究，探讨了外部 pH 值的变化如何影响梭菌丙酮丁醇乙醇（ABE）发酵途径。这一点特别有趣，因为最近生物燃料正丁醇的生物技术生产又回到了工业应用的焦点。一个前提是进一步了解决定溶剂生产的因素及其综合调控。我们已经从数学上分析了代谢分支点的 pH 依赖性特定酶活性对产物形成的影响。将这种动力学调节与转录组学调节（关于基因转录和蛋白质组学图谱）进行了比较。此外，还综合了这两种调控机制，详细预测了它们对产物形成的单独和联合作用。所得到的模型代表了基于丙酮丁醇梭菌的工业丁醇生产未来发展的重要平台。
