TAXOL PRODUCTION IN BIOREACTORS - KINETICS OF BIOMASS ACCUMULATION, NUTRIENT-UPTAKE, AND TAXOL PRODUCTION BY CELL-SUSPENSIONS OF TAXUS-BACCATA

The kinetics of biomass accumulation, nutrient uptake, and taxol production of Taxus baccata cell suspensions were examined in three bioreactor configurations, viz. 250-mL Erlenmeyer flasks, 1-L working volume pneumatically mixed (PMB), and stirred tank (STB) bioreactors. Qualitatively similar kinetics were observed in all three bioreactor types. Biomass accumulation and specific nutrient uptake rates exhibited biphasic characteristics. Carbohydrate uptake and biomass accumulation substantially ceased when phosphate was depleted from the medium. Phosphate was identified as a possible growth-limiting nutrient. Taxol accumulated exclusively in the second phase of growth. A maximum taxol concentration of 1.5 mg/L was obtained in the PMB which was fivefold greater than that obtained in the Erlenmeyer flasks and the STB, but the relative kinetics of taxol production was the same in all three reactor types. Biomass yields were calculated from the kinetic data and a stoichiometry for biomass formation was evaluated. The similarity of kinetics in the three bioreactor configurations suggests that taxol production by T. baccata cell suspensions is amenable to scaleup. (C) 1995 John Wiley & Sons, Inc.