Kreis W, Reinhard E
Pharmazeutisches Institut, Eberhard-Karls-Universität Tübingen, Germany.
J Biotechnol. 1992 Nov;26(2-3):257-73. doi: 10.1016/0168-1656(92)90011-w.
A biotransformation process for the production of digoxin was developed using Digitalis lanata cell suspension cultures. Digitoxin was used as the substrate for biotransformation. Digoxin production was carried out in a variety of vessels, including 1-l exsiccators, 20-l glass reactors and a 300-l air-lift bioreactor. A culture volume of 200 l was established after 28 d and the cells were then cultured semi-continuously in a 300-l bioreactor employing the draw-fill cultivation method. Maximal digoxin production was achieved in an 8% glucose medium with a production optimum after 40-60 h of incubation in the presence of 0.65-0.8 mmol digitoxin per l. Levels of 0.52, 0.53 and 0.60 mmol digoxin per l suspension were achieved in 1-l, 20-l and 300-l vessels, respectively. About 80% of the digoxin produced was found in the bathing medium.
利用毛花洋地黄细胞悬浮培养开发了一种生产地高辛的生物转化工艺。洋地黄毒苷用作生物转化的底物。地高辛生产在多种容器中进行，包括1升干燥器、20升玻璃反应器和300升气升式生物反应器。28天后建立了200升的培养体积，然后采用抽灌培养法在300升生物反应器中对细胞进行半连续培养。在含有0.65 - 0.8 mmol/升洋地黄毒苷的8%葡萄糖培养基中，孵育40 - 60小时后达到地高辛的最大产量。在1升、20升和300升容器中，每升悬浮液中地高辛的产量分别达到0.52、0.53和0.60 mmol。所生产的地高辛约80%存在于培养液中。
