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In fermentations with a 4-liter stirred tank bioreacto;a better than two-fold enhancement of the gas-liquid mass transfer coefficient (kLa) in the celite-immobilized fungal cultures of Tolypocladium inflatum over the parallel conventional free-cell was observed at identical biomass concentrations, despite the higher specific oxygen uptake rate of the immobilized fungi during exponential growth. As a result, oxygen sufficient conditions, i. e., dissolve oxygen (D. 0.) concentrations exceeding 75% air saturation, could be maintained throughout exponential growth period of the immobilized culture, in contrast to the suspended fungal culture, whose D. 0. levels fell below 150% air saturation. A linear monotonic dependence of k,,a upon impeller agitaion rate was found for both immobilized and conventional cultivation modes over a range of 250 to 550rpm, the slope being a function of biomass concentration for the free but not for the immobilized cell system. In contrast, oxygen transfer rate was a much weaker function of aeration rate up to about 2.5 vvm for both culture configurations. Above this level, aeration rate had no further effect on the mass transfer. In addition, the immobilized cultures sustained good morphological and physiological states, leading to almost two times higher cyclosporin A (CyA ) productivity over the parallel free cell system. These experiments suggest that the celite- immobilized fungal system in a stirred tank reactor has considerable promise for scaling up cyclosporin A production in terms of high-density cultivation.
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