HIGH-DENSITY CULTIVATION OF ANCHUSA-OFFICINALIS IN A STIRRED-TANK BIOREACTOR WITH IN-SITU FILTRATION

Previously, Su et al. [Biotechnol Bioeng 42: 884-890 (1993)] reported improved production of rosmarinic acid by Anchusa officinalis in shake -flask cultures using a cultivation strategy that involved intermitten t medium exchange. Implementation of this cultivation strategy in 2.5- 1 stirred-tank bioreactor cultures is investigated in the present stud y. Intermittent cell/medium separation in the bioreactor was accomplis hed by means of automated in situ culture filtration. In the bioreacto r culture, rosmarinic acid production was found very sensitive to agit ation and aeration conditions as well as dissolved oxygen concentratio n. A maximum cell density of 35 g dry weight/l and a rosmarinic acid c oncentration of 3.7 g/l were obtained by maintaining the dissolved oxy gen concentration above 30% air saturation, gradually raising the impe ller tip speed from 34 cm/s to 72 cm/s, and keeping the aeration rate at 0.44 vvm while increasing the O-2: air ratio in the gas feed stream to 4:1. This result is comparable with the data obtained from shake-f lask cultures using the same culture strategy.