Oxygen enriched air supply in Escherichia coli processes:: production of biomass and recombinant human growth hormone

Oxygen enriched air supply in Escherichia coli processes:: production of biomass and recombinant human growth hormone
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DOI:
10.1016/s0141-0229(01)00490-2
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发表时间:
2002-06-04
影响因子:
3.4
通讯作者:
Enfors, SO
Enfors, SO
中科院分区:
工程技术3区
文献类型:
--
作者:
Castan, A;Näsman, A;Enfors, SO

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为了研究高氧和高二氧化碳浓度对大肠杆菌的影响,在空气供应富集氧气或二氧化碳的情况下,对大肠杆菌进行了批量培养。用这种方法研究了氧气和二氧化碳浓度升高对化学计量常数和动力学常数的影响。与对照培养和富氧培养相比,富二氧化碳培养的最大生长率显著降低,乙酸产量和葡萄糖生物量产率系数显著提高。研究了富氧空气在大肠杆菌高密度培养中的应用。选择了两种生产工艺来研究富氧的影响。考察了重组产物的生物量浓度、特定生长率、产率系数、呼吸作用、混合酸发酵产物以及产率和质量。首先,对生物质的生产过程进行了研究。在富氧空气的供应下,可以维持较长时间的指数生长和较高的生长速度。然而,在富氧开始后,每葡萄糖的比耗氧率更高,表明维持率更高,因此在过程结束时生长速度和产率系数急剧下降。其次,研究了重组人生长激素(rhGH)的生产工艺。虽然葡萄糖的进料率和所有培养基成分增加了一倍,但当富氧空气(氧气含量为40%)供应时,产生的生物量只能增加77%。这是由于每葡萄糖的生物量产率系数降低。与对照相比,生产的产品总量减少了近50%,尽管产生了较少的蛋白质降解变体。(C) 2002爱思唯尔科学有限公司版权所有。
In order to investigate the impact of high oxygen and carbon dioxide concentrations, Escherichia coli was grown in batch cultivations where the air supply was enriched with either oxygen or carbon dioxide. The effect of elevated concentrations of oxygen and carbon dioxide on stochiometric and kinetic constants was studied this way. The maximum growth rate was significantly reduced, the production of acetic acid and the biomass yield coefficient on glucose increased in cultures with carbon dioxide enriched air, compared to reference cultivations and cultivations with oxygen enriched air. The application of oxygen enriched air was studied in high cell density cultivations of Escherichia coli. Two production processes were chosen to investigate the impact of oxygen enrichment. Biomass concentration, specific growth rate, yield coefficient, respiration, mixed acid fermentation products and the product yield and quality for the recombinant product were investigated. First, a process for the production of biomass was investigated. Exponential growth could proceed for a longer time and higher growth rates could be maintained with oxygen enriched air supply. However, a higher specific oxygen consumption rate per glucose was measured after the start of the oxygen enrichment, indicating higher maintenance and consequently the growth rate and yield coefficient decreased drastically in the end of the process. Second, a process for the production of recombinant human growth hormone (rhGH) was investigated. Although the glucose feed rate and all medium components were doubled, the amount of produced biomass could only be increased by 77% when oxygen enriched air (40% oxygen) supply was applied. This was due to a decreased yield coefficient of biomass per glucose. The total amount of produced product was decreased by almost 50% compared to the control, although less proteolytically degraded variants were produced. (C) 2002 Elsevier Science Inc. All rights reserved.