论文标题

建立和建模枯草芽孢杆菌的饲养批量培养物用于生产和连续去除脂肽

Setting up and modelling of overflowing fed-batch cultures of Bacillus subtilis for the production and continuous removal of lipopeptides

论文作者

Guez, J. S, Chenikher, S., Cassar, J. Ph, Jacques, P.

论文摘要

这项工作与源自碳有限的EFBC衍生的额定指数饲料批量培养(O-EFBC)的设置有关,该培养物用于生产Mycosubtilin,Mycosubtilin是一种属于Iturin家族的抗真菌脂肪肽。 O-EFBC允许从生物反应器中连续去除产物,从而完全提取了Mycosubtilin。本文还提供了该过程的基于动力学的单体增长模型,该模型足够准确,可以模拟特定的增长率的演变并将其与Mycosublitilin特定的生产率相关联。该模型考虑了与泡沫溢出有关的两个特定和依赖现象:肉汤体积的传出流速和生物量损失。有趣的是,发现泡沫中的生物量浓度低于生物反应器中的生物量浓度,将该过程与回收过程相关。该模型的参数是底物的生长产率和最大比以0.062、0.071和0.086 h -1的实验估计的特异性生长速率。该模型以0.008、0.022、0.040、0.042和0.062 h -1的进料速率进行了五个额外的实验,从而使平均特定生长速率与生产率结果的相关性。最后,饲料率为0.086 h -1,对应于平均比例为0.070 h -1的平均特异性生长速率允许干燥生物量H -1的Mycosubtilin g -1的特异性生产率为1.27 mg。

This work is related to the setup of overflowing exponential fed-batch cultures (O-EFBC) derived from carbon limited EFBC dedicated to the production of mycosubtilin, an antifungal lipopeptide belonging to the iturin family. O-EFBC permits the continuous removal of the product from the bioreactor achieving a complete extraction of mycosubtilin. This paper also provides a dynamical Monod-based growth model of this process that is accurate enough to simulate the evolution of the specific growth rate and to correlate it to the mycosubtilin specific productivity. Two particular and dependant phenomena related to the foam overflow are taken into account by the model: the outgoing flow rate of a broth volume and the loss of biomass. Interestingly, the biomass concentration in the foam was found to be lower than the biomass concentration in the bioreactor relating this process to a recycling one. Parameters of this model are the growth yield on substrate and the maximal specific growth rate estimated from experiments led at feed rates of 0.062, 0.071 and 0.086 h --1. The model was extrapolated to five additional experiments carried out at feed rates of 0.008, 0.022, 0.040, 0.042 and 0.062 h --1 enabling the correlation of the mean specific growth rates with productivity results. Finally, a feed rate of 0.086 h --1 corresponding to a mean specific growth rate of 0.070 h --1 allowed a specific productivity of 1.27 mg of mycosubtilin g --1 of dried biomass h --1 .

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