Physiological studies related to the immobilization of Penicillium chrysogenum and penicillin production.

Using the production of penicillin by Penicillium chrysogenum as a model system, certain physiological aspects of immobilized and free cell cultures were compared. Reducing the immobilized viable spore loading (from 4 x 10(4) to 2 x 10(3) spores ml-1 gel) and initial bead diameter (from 3.5-4.0 to 1.5-2.0 mm) gave rise to an increase in the penicillin titer from 0.2 to 1.2 g l-1. Using these conditions in immobilized cell culture the growth phase was prolonged and the duration of expression of the isopenicillin N synthase gene (pcbC) was significantly extended when compared with free cell culture (150 h as opposed to 100 h). During the period of maximum penicillin production, different penicillin biosynthetic intermediates accumulated in the broth of free and immobilized cell cultures, reflecting a fundamental difference in cell physiology. Although the maximum specific productivity of penicillin production was reduced by immobilization, the average specific productivity increased when compared to free cell fermentation.