Lequeux Gaspard, Beauprez Joeri, Maertens Jo, Van Horen Ellen, Soetaert Wim, Vandamme Erick, Vanrolleghem Peter A
Department of Applied Mathematics, Biometrics and Process Control, Ghent University, Coupure Links 653, 9000 Gent, Belgium.
J Biomed Biotechnol. 2010;2010. doi: 10.1155/2010/621645. Epub 2010 Aug 23.
The main requirement for metabolic flux analysis (MFA) is that the cells are in a pseudo-steady state, that there is no accumulation or depletion of intracellular metabolites. In the past, the applications of MFA were limited to the analysis of continuous cultures. This contribution introduces the concept of dynamic MFA and extends MFA so that it is applicable to transient cultures. Time series of concentration measurements are transformed into flux values. This transformation involves differentiation, which typically increases the noisiness of the data. Therefore, a noise-reducing step is needed. In this work, polynomial smoothing was used. As a test case, dynamic MFA is applied on Escherichia coli cultivations shifting from carbon limitation to nitrogen limitation and vice versa. After switching the limiting substrate from N to C, a lag phase was observed accompanied with an increase in maintenance energy requirement. This lag phase did not occur in the C- to N-limitation case.
代谢通量分析（MFA）的主要要求是细胞处于伪稳态，即细胞内代谢物没有积累或消耗。过去，MFA的应用仅限于连续培养的分析。本文介绍了动态MFA的概念，并对MFA进行了扩展，使其适用于瞬态培养。浓度测量的时间序列被转换为通量值。这种转换涉及微分，这通常会增加数据的噪声。因此，需要一个降噪步骤。在这项工作中，使用了多项式平滑。作为一个测试案例，动态MFA应用于从碳限制转变为氮限制以及反之亦然的大肠杆菌培养。将限制底物从氮切换为碳后，观察到一个延迟期，同时维持能量需求增加。在从碳限制到氮限制的情况下没有出现这个延迟期。
