Modelling, optimization and control of continuous two-stage Cephalosporin C production

Cephalosporin is one of the most consumed antibiotics for its effectiveness against a wide variety of infections. Most cephalosporin products are the semi-derivatives of Cephalosporin C (CPC), a metabolite of the fungus Acremonium chrysogenum. Since naturally the desired metabolite is not produced in a large amount by the fungus, an innovative operational strategy is required to increase its yield for the production of the antibiotic to be economically feasible. One way to increase the cephalosporin productivity is by increasing the concentration of thin hyphae cell in the bioreactor, but this will lead to a higher blower power requirement for providing adequate availability of oxygen in the fermentation broth. Lack of oxygen will retard the growth rate and reduce the productivity. Conversely, excessive aeration of the fermentation broth will lead to high shear stress that can kill the cells. The present work investigates through dynamic simulation the effectiveness of a continuous two-stage aerobic fermentation for the CPC production. The operating conditions are optimized to determine an optimal trade-off between the cephalosporin productivity and blower power. An increase of the dissolved oxygen in the first bioreactor from 10 % to 20 % can increase CPC productivity by 75.5 % from 24.42 mg/L.hr to 42.86 mg/L.hr.