Two-stage cultivation of Digitalis lanata cells: semicontinuous production of deacetyllanatoside C in 20-litre airlift bioreactors.

A two-stage cultivation method was employed to develop a semicontinuous biotransformation process for the production of deacetyllanatoside C, a cardenolide of the important digoxin series. Digitoxin was used as the substrate for biotransformation. The process was optimized in 1-l shake flasks and then established on the 20-l scale using two airlift bioreactors, one for cell growth (working volume 12 litres) and another for deacetyllanatoside C production (working volume 18 litres). Growth and production phases were synchronized and the process finally ran semicontinuously in 7-d cycles. Six consecutive production runs were performed yielding a total of 43.8 g deacetyllanatoside C.