STUDIES OF REPEATED FED-BATCH FERMENTATION OF CEPHALOSPORIN-C IN AN IMMOBILIZED CELL BIOREACTOR

Acremonium chrysogenum was immobilized in ionotropic gel beads to develop semi-continuous production of cephalosporin C (CPC). Barium alginate beads were more stable than calcium alginate or strontium alginate beads in chemically defined media. The gel stability of Ba-alginate was further increased by cross-linking with polyethyleneimine (PEI). The presence of carboxymethyl cellulose inside Ba-alginate beads did not reduce mass transfer resistance. Ba-alginate microbeads that had little diffusion limitation increased CPC production rate 1.6 fold higher than that of normal beads. CPC fermentation with immobilized cells in Ba-alginate microbeads was performed continuously for 40 days by way of repeated fed-batch operations. Mathematical modeling was developed to describe the repeated fed-batch fermentation system. Results of the computer simulation agreed well with the experimental data, which made it possible to predict an optimal feeding rate that could maximize total CPC productions.