Investigation of factors in the optimisation of penicillin production

Penicillin production trials were carried out in stirred 5-dm3 fermenters to collect data and investigate aspects of the process likely to be important in on-line optimisation. These included the calculation of growth from the production of carbon dioxide, the relation between age and productivity and the effect of dilution and culture replacement. Three types of media were used, a synthetic medium and complex commercial-type nutrient media based on corn-steep liquor or peanut meal together with a nutrient feed and pH control. All gave good results although the synthetic medium tended to show only transient production on some occasions. An equation was devised enabling the correct calculation of the growth curve from carbon dioxide output. It was found that the maintenance energy requirements (as indicated by CO2 production) were much higher with synthetic medium than with complex media. Decay curves (of Qpenvs time) were readily calculated using Shu's17 equation. The highest outputs of penicillin were obtained by dilution or replacement systems, but it was essential to start the process early when the penicillin-producing enzymes were active and stable. It was also necessary to supply glucose at an adequate rate, to hold dissolved oxygen concentration above 25% and avoid too high cell concentrations. It was concluded that theories of penicillin production based on feed-rate or dilution, or on the effect of age, are essentially complementary, both aspects being important in determining the optimal course of the fermentation.