Metabolic oscillations in an E-coli fermentation
Metabolic oscillations in an E-coli fermentation
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DOI：
10.1002/bit.10018
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发表时间：
2001-10-20
影响因子：
3.8
通讯作者：
Snedecor, B
中科院分区：
文献类型：
--
作者：
Andersen, DC;Swartz, J;Snedecor, B
重组大肠在受控发酵过程中，观察到大肠杆菌发酵在几个小时的氧摄取中经历规则的、可再现的振荡。在振荡期间，培养物生长减慢，延迟了重组蛋白生产的诱导。振荡在10-L和1，000-L发酵罐中相似，并且也发生在不同的进料控制算法中。这两个观察结果都支持了振荡本质上是代谢的假设。氨基酸，ATP，和GTP池的分析表明，振荡的结果从异亮氨酸生物合成的异常调节，导致重复的饥饿事件，其中蛋白质合成和生长受损。营养解决方案，异亮氨酸喂养，和遗传解决方案，修复E. coliK-12菌株，发现消除振荡，进一步支持所提出的机制的行为。这些结果说明了有趣的和复杂的生理行为，可以显示在代谢网络，并提供了另一个例子，令人惊讶的问题，可以出现在发酵罐中的重组生物体的生长。(C)John Wiley & Sons，Inc.
Recombinant E. coli fermentations were observed to undergo regular, reproducible oscillations in oxygen uptake for several hours during a controlled fermentation process. Culture growth slowed during the period of oscillations, delaying induction of recombinant protein production. The oscillations were similar in 10-L and 1,000-L fermentors and also occurred with different feed control algorithms. Both observations support the hypothesis that the oscillations are metabolic in nature. Analysis of amino acid, ATP, and GTP pools suggests that the oscillations result from aberrant regulation of isoleucine biosynthesis leading to repeated starvation events in which protein synthesis and growth are impaired. Both a nutritional solution, isoleucine feeding, and a genetic solution, repair of an ilvG frameshift mutation in E. coli K-12 strains, were found to eliminate the oscillations, further supporting the proposed mechanism for the behavior. These results illustrate the interesting and complicated physiological behavior which can be displayed in metabolic networks and provide another example of surprising problems that can arise in growing recombinant organisms in fermentors. (C) 2001 John Wiley & Sons, Inc.