A model for penicillin production with and without temperature shift after the growth phase.

A strain of Penicillium chrysogenum producing about 8 milligrams/l of penicillin V, was cultivated in a 10-1 bioreactor. Under carbon (C)-limitation during the production phase a glucose/ammonium sulphate mixture was fed using microprocessor control. When the temperature was shifted from 25 degrees C to 30 degrees C at the end of the active growth phase, the specific penicillin production rate was increased by 30%, while the yield remained constant. Maximal productivity without sporulation was obtained when the net growth rate of the active (respiring and producing) biomass, estimated by measuring the respiration rate under defined conditions, was equal to or higher than 0.004 h-1. A model was developed for penicillin fermentation during C-limitation possessing the following properties: (1) the model is based on ordinary differential equations; (2) the influence of different nutrients is considered; (3) the model recognizes two cell types (active and inactive); (4) the model describes the influence of a temperature shift at the end of the vigorous growth phase.