Biosynthesis of podophyllotoxin in Linum album cell cultures

Veronique Seidel, Jorg Windhövel, Graham Eaton, A. Wilhelm Alfermann, Randolph R.J. Arroo, Manuel Medarde, Maike Petersen, Jack G. Woolley

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66 Citations (Scopus)


Cell cultures of Linum album Kotschy ex Boiss. (Linaceae) showing high accumulation of the lignan podophyllotoxin (PTOX) were established. Enzymological studies revealed highest activities of phenylalanine ammonia-lyase, cinnamyl alcohol dehydrogenase, 4-hydroxycinnamate:CoA ligase and cinnamoyl-CoA:-NADP oxidoreductase immediately prior to PTOX accumulation. To investigate PTOX biosynthesis, feeding experiments were performed with [2- 13 C]3¢,4¢-dimethoxycinnamic acid, [2-13 C]3¢,4¢-methylenedioxycinnamic acid (MDCA), [2-13C]3¢,4¢,5¢-trimethoxycinnamic acid,[2- 13C]sinapic acid, [2-13C]- and [2,3-13C2]ferulic acid.Analysis of the metabolites by HPLC coupled to tandem mass spectrometry revealed incorporation of label from ferulic acid into PTOX and deoxypodophyllotoxin (DOP). In addition, MDCA was also unambiguously incorporated intact into PTOX. These observations suggest that in L. album both ferulic acid and methylenedioxy-substituted cinnamic acid can be incorporated into lignans. Furthermore, it appears that, in this species, the hydroxylation of DOP is a rate-limiting point in the pathway leading to PTOX.
Original languageEnglish
Pages (from-to)1031-1039
Number of pages9
Issue number6
Publication statusPublished - 1 Oct 2002


  • podophyllotoxin
  • biosynthesis
  • linum album


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