50L罐头孢菌素C发酵过程豆油流加控制策略的优化

Optimization of soybean oil feeding strategy for cephalosporin C fermentation conducted in 50L bioreactor

目的优化头孢菌素C(CPC)发酵过程的豆油补料控制策略,提高发酵整体性能。方法提出了一种匀速+DO-Stat结合型补油策略。在50L罐上对使用该策略和使用匀速补油以及传统DO-Stat自动补油策略的发酵性能进行比较,确定最优补油控制策略。结果采用匀速+DO-Stat结合型补油策略时,CPC终浓度最高,CPC得率也从使用匀速补油策略时的19.61%提高到25.74%,代谢主副产物去乙酰氧头孢菌素C(DAOC)的积累量少,DAOC/CPC(W/W)只有0.46%,达到生产要求。结论使用匀速+DO-Stat结合型补油策略,可控制CPC发酵过程中的碳源浓度和溶解氧浓度(DO)于合适水平,在维持较高的CPC生产强度的前提下,CPC得率大幅提高,代谢副产物的积累得到抑制、产品质量得到控制。

Objective Optimizing soybean oil feeding strategy to improve the overall cephalosporin C （CPC） fermentation performance. Methods A novel and automatic soybean oil feeding strategy combining constant feeding and DO-Stat feeding （constant＋DO-Stat feeding） was proposed and applied in CPC fermentation in 50L bioreactor. Fermentation performance utilizing different soybean oil feeding strategies, namely, constant feeding, DO-Stat based feeding and the proposed constant＋DO-Stat feeding was compared, and the optimal feeding strategy was determined. Results When using the constant＋DO-Stat feeding strategy, final CPC concentration was the highest; CPC yield was largely increased from 19.50% when adopting the constant feeding strategy to 25.74%; less deacetoxycephalosporin C （DAOC）, the major by-product of CPC fermentation, was accumulated; DAOC/CPC （W/W） stayed at low level of 0.46% satisfying with the industrial standard. Conclusion The newly proposed constant＋DO-Stat feeding strategy could control both carbon source concentration and DO at adequate levels simultaneously, CPC yield was largely increased and DAOC accumulation was significantly repressed, while CPC productivity was maintained at comparably high level.