Department of Biotechnology, Bioprocess Engineering, Technische Universität Berlin, Berlin, Germany.
Research Centre Juelich, IBG-1-Institute of Bio- and Geosciences, Biotechnology, Juelich, Germany.
Biotechnol Prog. 2019 May;35(3):e2804. doi: 10.1002/btpr.2804. Epub 2019 Mar 23.
Corynebacterium glutamicum is well-known as an industrial workhorse, most notably for its use in the bulk production of amino acids in the feed and food sector. Previous studies of the effect of gradients in scale-down reactors with complex media disclosed an accumulation of several carboxylic acids and a parallel decrease of growth and product accumulation. This study, therefore, addresses the impact of carboxylic acids, for example, acetate and l-lactate, on the cultivation of the cadaverine producing strain C. glutamicum DM1945Δact3:P -ldcC and their potential role in scale up related performance losses. A fluctuating power input in shake flask and stirred tank cultivations with mineral salt was applied to mimic discontinuous oxygen availability. Results demonstrate, whenever sufficient oxygen was available, C. glutamicum recovered from previously occurring stressful conditions like an oxygen limiting phase. Reassimilation of acids was detected simultaneously. In cultures, which were supplemented with either acetate or l-lactate, a rapid cometabolization of both acids in presence of glucose was observed, showing conversion rates of 7.8 and 3.8 mmol g hr , respectively. Uptake of these acids was accompanied by increased oxygen consumption. Proteins related to oxidative stress response, glycogen synthesis, and the main carbon metabolism were found in altered concentrations under oscillatory cultivation conditions. (Proteomics data are available via ProteomeXchange with identifier PXD012760). Virtually no impact on growth or product formation was observed. We conclude that the reduced growth and product formation in scale-down cultivations when complex media was used is not caused by the accumulation of carboxylic acids.
谷氨酸棒杆菌是一种众所周知的工业生产用菌，特别是在饲料和食品行业中大量生产氨基酸方面。以前的研究表明，在具有复杂介质的缩小规模反应器中梯度的影响会导致几种羧酸的积累，同时生长和产物积累会减少。因此，本研究探讨了羧酸（例如乙酸和 L-乳酸）对产腐胺菌株 C. glutamicum DM1945Δact3:P -ldcC 的培养的影响及其在放大相关性能损失中的潜在作用。在摇瓶和搅拌罐培养中应用波动的功率输入来模拟不连续的氧气可用性。结果表明，只要有足够的氧气，C. glutamicum 就可以从以前出现的应激条件（例如缺氧阶段）中恢复。同时检测到酸的再同化。在补充了乙酸或 L-乳酸的培养物中，观察到在葡萄糖存在下这两种酸的快速共代谢，转化率分别为 7.8 和 3.8 mmol g hr。这些酸的吸收伴随着耗氧量的增加。在振荡培养条件下，与氧化应激反应、糖原合成和主要碳代谢相关的蛋白质的浓度发生了改变。（蛋白质组学数据可通过 ProteomeXchange 以标识符 PXD012760 获得）。几乎没有观察到对生长或产物形成的影响。我们得出结论，在使用复杂介质的缩小规模培养中，生长和产物形成减少不是由于羧酸的积累引起的。
