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Importance of the cultivation history for the response of Escherichia coli to oscillations in scale-down experiments

机译：在小规模实验中培养历史对大肠杆菌对振荡响应的重要性

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摘要

Large-scale bioreactors are inhomogeneous systems, in which the fluid phase expresses concentration gradients. They depend on the mass transfer and fluid dynamics in the reactor, the feeding strategy, the cell-specific substrate uptake parameters, and the cell density. As high cell densities are only obtained at low specific growth rates, it is necessary to investigate the cellular responses to oscillations in particular under such conditions, an issue which is mostly neglected. Instead, the feed oscillations are often started directly after the batch phase, when the specific growth rate is close to the maximum. We show here that the cultivation mode before oscillations are started has a tremendous effect on the metabolic responses. In difference to cells, which were pre-grown under batch conditions at a high growth rate, Escherichia coli cells that were pre-grown under glucose limitation at a low growth rate accumulate short-chain fatty acids (acetate, lactate, succinate) and glycolysis-related amino acids to a higher extent in a two-compartment scale-down bioreactor. Thus, cells which enter oscillations from a lower specific growth rate seem to react more sensitive to oscillations than cells that are subjected to oscillations directly after a batch phase. These results are interesting in designing reliable scale-down systems, which better reflect large-scale bioprocesses.
机译：大型生物反应器是不均匀的系统，其中液相表达浓度梯度。它们取决于反应器中的传质和流体动力学，进料策略，特定细胞的底物摄取参数以及细胞密度。由于只有在低的特定生长速率下才能获得高细胞密度，因此有必要研究细胞对振荡的反应，特别是在这种条件下，这一问题通常被忽略。取而代之的是，当比生长速率接近最大值时，饲料振荡通常在分批阶段之后立即开始。我们在这里显示出振荡开始之前的培养模式对代谢反应具有巨大影响。与在批量条件下以高生长速率预生长的细胞不同，在葡萄糖限制下以低生长速率预生长的大肠杆菌细胞会积累短链脂肪酸（乙酸盐，乳酸盐，琥珀酸盐）和糖酵解两室按比例缩小的生物反应器中更高程度地相关氨基酸。因此，与在批处理阶段之后直接经受振荡的细胞相比，以较低的比生长速率进入振荡的细胞似乎对振荡更敏感。这些结果在设计可靠的按比例缩小系统方面很有意思，该系统可以更好地反映大规模生物过程。

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