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首页> 外文期刊>Bioprocess and Biosystems Engineering >Assessment of robustness against dissolved oxygen/substrate oscillations for C. glutamicum DM1933 in two-compartment bioreactor
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Assessment of robustness against dissolved oxygen/substrate oscillations for C. glutamicum DM1933 in two-compartment bioreactor

机译：评估两室生物反应器中谷氨酸棒杆菌DM1933对溶解氧/底物振荡的鲁棒性

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摘要

Corynebacterium glutamicum is an important organism for industrial biotechnology; particularly, in amino acid production (e.g. L-lysine). Production scales often reach reactor working volumes of several hundred cubic meters, which triggers inhomogeneous distribution of substrates and dissolved gasses due to increasing mixing times. Individual cells which follow the flow profile through the reactor are experiencing oscillating microen-vironments. Oscillations can have an influence on the process performance, which is a subject of scale-down experiments. In this work, L-lysine-producing C. glutamicum DM1933 was assessed for its robustness against continuous dissolved oxygen and substrate supply oscillation in two-compartment scale-down bioreactors. Aerobic, substrate-limited stirred tank and non-aerated, substrate-excess plug flow compartments were applied for oscillation. Inhomogeneity of substrate and oxygen supply was observed to cause rapid side product turnover, redistribution of oxygen uptake from oxygen limited into fully aerobic zones, and intermediate medium acidification. However, process inhomogeneity did not impair productivity or growth at plug flow residence times of several minutes. In a focused analysis of proteome, metabolome, transcriptome, and other physiological parameters, no changes were identified in response to process inhomogeneity. In conclusion, fed-batch processes with C. glutamicum DM1933 possess remarkable robustness against oxygen and substrate supply oscillation, which is a unique property in the field of published scale-down studies. Microbial physiology of C. glutamicum appears to be ideally adapted to both homogeneous and inhomogeneous conditions. This ensures exceptional suitability for cultivation at increased mixing times, which is suggested to constitute an important basis for the long-lasting success in large scale bioprocess application.
机译：谷氨酸棒杆菌是工业生物技术的重要生物。特别是在氨基酸生产（例如L-赖氨酸）中。生产规模通常达到数百立方米的反应器工作量，由于混合时间的增加，这会触发底物和溶解气体的不均匀分布。遵循通过反应器的流量分布的单个单元正在经历振荡的微环境。振荡可能会对过程性能产生影响，这是按比例缩小实验的主题。在这项工作中，评估了产生L-赖氨酸的谷氨酸棒杆菌DM1933在两室按比例缩小的生物反应器中对连续溶解氧和底物供应波动的抵抗力。需氧，受底物限制的搅拌槽和未充气，底物过量的活塞流室用于振荡。观察到底物和氧气供应的不均匀性会导致副产物快速流动，限制了进入完全好氧区域的氧气吸收的氧气重新分布，以及中间介质酸化。但是，在几分钟内的活塞流停留时间，工艺的不均匀性不会损害生产率或生长。在蛋白质组，代谢组，转录组和其他生理参数的集中分析中，未发现对过程不均一性的变化。总之，谷氨酸棒杆菌DM1933的分批补料工艺对氧气和底物供应振荡具有显着的鲁棒性，这在已发表的按比例缩小研究领域中是独特的。谷氨酸棒杆菌的微生物生理学似乎理想地适用于均质和非均质条件。这确保了在增加混合时间时特别适合种植，这被认为是大规模生物工艺应用中持久成功的重要基础。

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  • 来源
    《Bioprocess and Biosystems Engineering》 |2014年第6期|1151-1162|共12页
  • 作者

    Friedrich Kaess; Ioanna Hariskos; Andrea Michel; Hans-Juergen Brandt; Robert Spann; Stefan Junne; Wolfgang Wiechert; Peter Neubauer; Marco Oldiges;

  • 作者单位

    Institute of Bio- and Geosciences, IBG-1: Biotechnology, Systems Biotechnology, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany;

    Institute of Bio- and Geosciences, IBG-1: Biotechnology, Systems Biotechnology, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany;

    Institute of Bio- and Geosciences, IBG-1: Biotechnology, Systems Biotechnology, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany;

    Institute of Bio- and Geosciences, IBG-1: Biotechnology, Systems Biotechnology, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany;

    Bioprocess Engineering, Department of Biotechnology, Technische Universitaet Berlin, Ackerstrasse 71-76, 13355 Berlin, Germany;

    Bioprocess Engineering, Department of Biotechnology, Technische Universitaet Berlin, Ackerstrasse 71-76, 13355 Berlin, Germany;

    Institute of Bio- and Geosciences, IBG-1: Biotechnology, Systems Biotechnology, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany;

    Bioprocess Engineering, Department of Biotechnology, Technische Universitaet Berlin, Ackerstrasse 71-76, 13355 Berlin, Germany;

    Institute of Bio- and Geosciences, IBG-1: Biotechnology, Systems Biotechnology, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Scale-down; Process inhomogeneity; Oxygen limitation; STR-PFR;

    机译：缩小;工艺不均匀;氧气限制STR-PFR;

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