12 beta-Hydroxylation of digitoxin by suspension-cultured Digitalis lanata cells: production of digoxin in 20-litre and 300-litre air-lift bioreactors.
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.
Kreis
W
W
Pharmazeutisches Institut, Eberhard-Karls-Universität Tübingen, Germany.
Reinhard
E
E
D000388:Air; D001709:Biotechnology / Q000295:instrumentation / Q000379:methods; D001711:Biotransformation; D004070:Digitalis / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D004074:Digitoxin / Q000378:metabolism* / Q000493:pharmacokinetics; D006900:Hydroxylation; D010946:Plants, Medicinal; D010947:Plants, Toxic; D013535:Suspensions; D013696:Temperature
D013535:Suspensions; D004074:Digitoxin