Tan Xin, Li Chao, Guo Meijin
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Shanghai Jianqi Biotechnology Co. Ltd., Shanghai 201400, China.
Sheng Wu Gong Cheng Xue Bao. 2022 Dec 25;38(12):4692-4704. doi: 10.13345/j.cjb.220292.
Erythromycin is a macrolide antibiotic produced by . Its yield is greatly affected by the fermentation conditions and the bioreactor configurations. In this study, a novel scale-up method for erythromycin fermentation was developed based on computational fluid dynamics (CFD) and time constant analysis. Firstly, the dissolved oxygen (DO) was determined as a key parameter according to the physiological properties of . cultivated in a 50 L bioreactor. It was found that the time constant of oxygen supply () in a 500 m bioreactor should be less than 6.25 s in order to satisfy the organism's oxygen uptake rate (OUR). Subsequently, a 500 m bioreactor was designed using the time constant method combined with empirical correlations. The impeller combination with one BDT8 impeller at bottom and two MSX4 impellers at upper part was determined, and then validated by numerical simulation. The results indicated that the of the bioreactor (< 6.25 s) and the fluid properties, including gas hold-up, shear stress and fluid vector, met the requirements of erythromycin fermentation. Finally, the industrial production of erythromycin in the 500 m showed the design method was applicable in large scale fermentation.
红霉素是由……产生的一种大环内酯类抗生素。其产量受发酵条件和生物反应器配置的影响很大。在本研究中，基于计算流体动力学（CFD）和时间常数分析，开发了一种新的红霉素发酵放大方法。首先，根据在50 L生物反应器中培养的……的生理特性，确定溶解氧（DO）为关键参数。发现500 m³生物反应器中氧气供应的时间常数（……）应小于6.25 s，以满足生物体的氧摄取率（OUR）。随后，采用时间常数法结合经验关联式设计了500 m³生物反应器。确定了底部一个BDT8叶轮和上部两个MSX4叶轮的叶轮组合，然后通过数值模拟进行了验证。结果表明，生物反应器的……（< 6.25 s）以及包括气含率、剪切应力和流体矢量在内的流体特性满足红霉素发酵的要求。最后，在500 m³生物反应器中进行红霉素的工业化生产表明该设计方法适用于大规模发酵。
