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Biotechnol Prog. 2019 Mar 9:e2804. doi: 10.1002/btpr.2804. [Epub ahead of print]

Carboxylic acid consumption and production by Corynebacterium glutamicum.

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Department of Biotechnology, Bioprocess Engineering, Technische Universität Berlin, Berlin, Germany.
Research Centre Juelich, IBG-1-Institute of Bio- and Geosciences, Biotechnology, Juelich, Germany.
Department of Molecular Biotechnology, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen, Germany.


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:Ptuf -ldcCopt 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 gcell dry weight -1 hr-1 , 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.


Corynebacterium glutamicum; carboxylic acid; heterogeneity; oxygen oscillation; scale down


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