CFD Simulation And Cephalosporin C Fermentation Performance Comparison With Different Impeller Combinations

Cephalosporin C(CPC) is an important intermediate for the production of β-lactam antibiotics,which is synthesized as a secondary metabolite by Cephalosporium acremonium featured withbyssoid and intensively oxygen demands. CPC can be modified through chemical orenzymatic methods into different synthetic and semi-synthetic cephalosporin. It is then usedto produce β-lactam antibiotics with low toxic effects and broad antibacterial spectrum.CPC plays an important role in the global pharmaceutical market. CPC fermentation is anextensive oxygen-consuming process together with high viscosity, its performance isdominated by mass transfers in bioreactor, including those of nutrient substance and oxygen.In this thesis, numerical simulation and experimental CPC fermentation were carried outsimultaneously to explore the relationship in between the flow field inside bioreactor andCPC fermentation performance.In the first part, simulations of the gas-liquid two-phase flow field for six different impellercombinations in a7L bioreactor using Computational Fluid Dynamics software FLUENTwere conducted. Then, by analyzing and comparing flow pattern, velocity field, shear ratedistribution, radial and axis velocities in the relevant indicatrix, two impeller combinationswith better mass transfer and mixing effects were selected. In the second part, the two selectedimpeller combinations and the original combination set in the bioreactor were utilized toconduct CPC fermentation experiments. By analyzing the important on-line and off-linevariables reflecting CPC fermentation performance, the optimal impeller combination forCPC fermentation was determined. The main contents of the thesis were summarized asfollows:1) The flow field in bioreactor was closely related with the distance between reactor bottom tobottom-impeller, distance between adjacent impellers, impellers shapes and their combination.Three layers combination had larger high-speed area than that of two layers combination, andincreasing attitude of the high-speed area was more significant than that of two layerscombination when agitation speed increasing from400r/min to800r/min.2) The dead-zone in bottom of bioreactor may be formed by the fluid flow pattern, air-holdingcharacter of the disk of bottom-impeller, and the interaction of gas-liquid phase. Certain radialflow in bottom region can reduce the dead-zone.3) In main CPC production phase when using DO-Stat method for soybean addition, the“platform effect” in DO occurred which deteriorated the rates of CPC synthesis and cellsgrowth in turn. Adopting a better impeller combination with good mass transfer and mixingeffect could eliminate the “platform effect” and improve fermentation performance.4) Cephalosporium acremonium is sensitive to shear rate. It is found that hypha of the fungicould be demaged irreversibly by extra shear rate in the early/middle CPC fermentationphases, which resulted a bad hypha differentiation and decreased CPC production. Thus,controlling shear rate in bioreactor during the early/middle phases was very important.In summary, improvement of mass transfer and mixing features in bioreactor couldsignificantly increase CPC fermentation performance. The performance improvement could be reflected by observing DO changing patterns, soybean oil feeding amount, the myceliamorphology, specific growth rate, CPC productivity and yield, and the major by-productDAOC (deacetoxycephalosporin) concentration. The fermentation performance of batch II isbetter than the other two batches. The CPC concentration improved for twice(33.29g/L) andDAOC concentration reduced to29%(0.18g/L) than the original impeller combination, whichgreatly improved the entire fermentation performance in turn.