Penicillium chrysogenum strain P1 was grown on complex media in 10 and 100 L agitated fermenters at various aeration rates and stirrer speeds. Samples were removed at intervals for measurements of the culture morphology. At high stirrer speeds (1000 and 1200 rpm) in 10-L fermentations the rate of decrease in the mean effective hyphal length was faster and the rate of penicillin production was lower than fermentations done at 800 rpm. At similar power inputs per unit volume in 100-L fermentations, the change in mean effective hyphal length was less and higher penicillin production rates were observed. This work comparing the results at two scales has shown that neither of the concepts of impeller tip speed or the dissipation rate of turbulence have general validity as a measure of hyphal damage. Our results are reasonaby well correlated by groups similar to circulation rate (ND(i) (3)/V) with lower circulation rates being beneficial. An adaptation of the van Suijdam and Metz relationship, expressed as P/D(i) (3)t(c), was most successful. Our data are insufficient to demonstrate the generality of the relationship but do support the concept of a dispersion zone around the impellers in which mycelia may be damaged. The greater the frequency of circulation of mycelia through the zone the greater the damage and the lower the rate of penicillin synthesis by the culture.

In situ product removal (ISPR) is the fast removal of product from a producing cell thereby preventing its subsequent interference with cellular or medium components. Over the past 10 years ISPR techniques have developed substantially and its feasibility (with improvements in yield or productivity) for several processes demonstrated. Assessment of progress, however, compared to the potential benefits inherent in the ISPR approach to bioprocessing reveals that these are far from being exploited fully. Here we indicate future directions including application of the ISPR approach to a wider range of product groups and the development of novel, more specific ISPR methodologies, applicable under sterile conditions in the immediate vicinity of the producing cells. General guidelines for adaptation of an appropriate ISPR approach for a given product are also provided.

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