SCALEUP OF AJMALICINE PRODUCTION BY PLANT-CELL CULTURES OF CATHARANTHUS-ROSEUS

The effects of scaleup on the production of ajmalicine by a Catharanthus roseus cell suspension culture in a selected induction medium were studied. In preliminary experiments it was observed that the culture turned brown and the production was inhibited upon transfer from a shake flask to a stirred bioreactor with forced aeration. Two factors were recognized as the potential origin of the differences between shake flask and bioreactor cultures: gas composition and mechanical shear forces. These factors were studied separately. By recirculating a large part of the exhaust gas, a comparable gas regime was obtained in a bioreactor as occurred in shake flask cultures. This resulted in the absence of browning and a similar pattern of ajmalicine production as observed in shake flasks. The effect of shear forces could not be demonstrated. However, the experiments showed that the culture may be very sensitive to liquid phase concentrations of gaseous compounds. The effects of k(L)a, aeration rate, CO2 production rate, and influent gas phase CO2 concentrations on the liquid phase CO2 concentration are discussed.