Semicontinuous and continuous production of penicillin-G by Penicillium chrysogenum cells immobilized in kappa-carrageenan beads.

Conidia of Penicillium chrysogenum were immobilized in K-carrageenan beads and then incubated in a growth-supporting medium to yield a penicillin producing immobilized cell mass. These in situ grown immobilized cells were used for the semicontinuous (replacement cultures)and continuous (fluidized bioreactor culture) production of penicillin-G. When periodically replaced into a minimal production medium, immobilized cells exhibited a half-life for penicillin production which was ninefold greater than that exhibited by free cells. The half-life of penicillin production and the yield of penicillin from glucose in such a replacement culture were greatly affected by the frequency of replacement and by the production medium's pH and concentration of glucose, phosphate, and trace metal nutrients. A penicillin-producing continuous flow bioreactor (150 mL), employing immobilized cells, was operated for up to 16 days. The best specific penicillin productivity (1.2 mg/g cells/h)yield from glucose (7.0 mg/g glucose) and half-life of production (15 days) were obtained when the feed medium contained 10 g/L of glucose, the pH was maintained at 7.0, the relative dissolved oxygen concentration was ca. 40%; and the residence time was 20 h.