Study of podophyllotoxin biosynthesis in Podophyllum species

Lignans are a structurally diverse group of phenylpropanoid metabolites widely distributed throughout the plant kingdom. Their biogenetic pathway has generally been viewed to occur via coupling of two monomeric moieties, with subsequent modifications as required to afford the various Iignan skeleton structures. Podophyllotoxin is a tetrahydronaphthalene lignan found in Podophyllum species, and its derivative etoposide is widely used medicinally for skin cancer and venereal warts (Condyloma acuminatum).

In this investigation, the biogenetic pathway to podophyllotoxin was investigated using whole plants, as well as callus and rhizome tissue. In contrast to previous claims in the literature, no active metabolism leading to podophyllotoxin formation in vivo in callus culture was observed. Similar findings were also noted for rhizome tissue. With whole plants, experiments investigating podophyllotoxin formation have been limited to employing lignan substrates, labeled specifically with carbon-14 and tritium. No stable isotopes, e.g carbon-13 or deuterium, have been used because of low incorporations.