Process performance of parallel bioreactors for batch cultivation of Streptomyces tendae
Process performance of parallel bioreactors for batch cultivation of Streptomyces tendae
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DOI：
10.1007/s00449-010-0471-1
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发表时间：
2011-03-01
影响因子：
3.8
通讯作者：
Weuster-Botz, Dirk
中科院分区：
文献类型：
--
作者：
Hortsch, Ralf;Krispin, Harald;Weuster-Botz, Dirk
在三种不同的平行生物反应器系统（毫升规模的搅拌罐反应器、摇瓶和摇动的微量滴定板）中进行尼可霉素Z生产者Streptomyces tendae的分批培养，并与作为参考的标准升规模的搅拌罐反应器进行比较。在搅拌罐反应器和摇瓶中，作为处理时间的函数，测量了相似的干细胞重量浓度，而在摇动的微量滴定板中仅观察到较差的生长。相比之下，尼可霉素Z的生产在搅拌和摇动的生物反应器之间显著不同。在不同规模的搅拌釜式反应器中，测得的产物浓度和产物生成动力学基本相同。在摇瓶和MTP培养中形成的尼可霉素Z少得多，最可能是由于氧气限制。为了研究小型生物反应器中培养液的非牛顿剪切稀化行为，采用一种新的简单方法来估算其流变行为。发现搅拌罐生物反应器中的表观粘度非常相似，而由于该反应器系统的平均剪切速率较低，摇瓶培养中的表观粘度增加了两倍。这些数据表明，应用于工艺开发的平行生物反应器的不同工程特性可能对使用非牛顿粘性培养液的生物工艺的规模化具有重大影响。
Batch cultivations of the nikkomycin Z producer Streptomyces tendae were performed in three different parallel bioreactor systems (milliliter-scale stirred-tank reactors, shake flasks and shaken microtiter plate) in comparison to a standard liter-scale stirred-tank reactor as reference. Similar dry cell weight concentrations were measured as function of process time in stirred-tank reactors and shake flasks, whereas only poor growth was observed in the shaken microtiter plate. In contrast, the nikkomycin Z production differed significantly between the stirred and shaken bioreactors. The measured product concentrations and product formation kinetics were almost the same in the stirred-tank bioreactors of different scale. Much less nikkomycin Z was formed in the shake flasks and MTP cultivations, most probably due to oxygen limitations. To investigate the non-Newtonian shear-thinning behavior of the culture broth in small-scale bioreactors, a new and simple method was applied to estimate the rheological behavior. The apparent viscosities were found to be very similar in the stirred-tank bioreactors, whereas the apparent viscosity was up to two times increased in the shake flask cultivations due to a lower average shear rate of this reactor system. These data illustrate that different engineering characteristics of parallel bioreactors applied for process development can have major implications for scale-up of bioprocesses with non-Newtonian viscous culture broths.