Effect of Growth Rate on the Synthesis of Penicillin by Penicillium chrysogenum in Batch and Chemostat Cultures.

The kinetics of penicillin production by Penicillium chrysogenum Wis 54-1255 in a glucose-limited chemostat and in batch cultures are reported. The specific production rate of penicillin, q(pen) (units per milligram of dry weight per hour) was independent of specific growth rate over the range 0.014 to 0.086 hr. Growth was stopped by restricting the glucose supply to the "maintenance ration," that is, the glucose requirement of the organism at zero growth rate with all other nutrients in excess. Under such conditions, the organism dry weight remained constant, but the q(pen) fell approximately linearly to zero at a rate inversely related to the previous growth rate. Glucose supplied in excess of the maintenance ration inhibited the decay of q(pen). At a critical growth rate between 0.009 and 0.014 hr, the decay was completely inhibited. Quantitative expressions for the q(pen) of growing and nongrowing cultures were derived and used to predict the steady-state concentrations of penicillin accumulating in one- and two-stage continuous processes. A rational explanation of the kinetics of penicillin accumulation in batch cultures is given, relating the rate of penicillin synthesis to growth rate. It is concluded that an important role of corn steep liquor (CSL), a heterogeneous carbon and nitrogen source commonly used in penicillin production media, is the provision of substrates which allow a high concentration of mold to be reached before the growth rate falls below the critical value. CSL had no significant effect on q(pen).