This cytochrome P-450 enzyme, characterized from the plant Sinopodophyllum hexandrum, produces the direct precursor to etoposide, a potent anticancer drug. It can also act on (-)-deoxypodophyllotoxin with lower efficiency.
the enzyme is involved in the biosynthesis of (-)-4'-demethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor. Biosynthetic pathway of (-)-podophyllotoxin, overview
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gene CYP82D61, expression analysis by qRT-PCR analysis, transcriptome mining to identify biosynthetic genes in the podophyllotoxin pathway, Agrobacterium-mediated functional transient expression in Nicotiana benthamiana
recombinant coexpression of the genes involved in the podophyllotoxin pathway permits to reconstitute the pathway to (-)-4'-demethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor, for production of the etoposide aglycone in tobacco and circumvent the need for cultivation of mayapple and semisynthetic epimerization and demethylation of podophyllotoxin