The production of podophyllotoxin and its 5-methoxy derivative through bioconversion of cyclodextrin-complexed desoxypodophyllotoxin by plant cell cultures

The bioconversion of the lignan desoxypodophyllotoxin by cell suspensions of Linum flavum and of Podophyllum hexandrum was investigated. The apolar substrate could be easily dissolved in the culture medium at a concentration of 2 mM by complexation with dimethyl-β-cyclodextrin. Growth parameters of the cell suspensions were not affected by either the addition of cyclodextrin itself, or when cyclodextrin-complexed desoxypodophyllotoxin was present in the medium. The complexed lignan disappeared from the medium within 7 days for both cell cultures. Cellularly only small amounts of desoxypodophyllotoxin were found. After feeding of desoxypodophyllotoxin, the cell culture of L. flavum accumulated 5-methoxypodophyllotoxin and 5-methoxypodophyllotoxin-β-D-glucoside. After 7 days a total maximal content of 2.38% on a dry weight basis of 5-methoxypodophyllotoxin was formed. corresponding with 249 mg l-1 suspension. The highest bioconversion percentage of 52.3% was found at day 14. The desoxypodophyllotoxin-fed culture of P. hexandrum accumulated podophyllotoxin and its β-D-glucoside with a maximal content of 2.87% on a dry weight basis after 9 days, corresponding with 192 mg l-1 suspension. The highest bioconversion percentage of 33.2% was also found at day 9.