[Review on biosynthesis of podophyllotoxin]

Podophyllotoxin (PTOX) is an extremely important plant-derived natural product, of which derivatives, like etoposide and teniposide, have been widely applied in therapies for cancers and venereal wart. A durable, intense plant extraction of podophyllotoxin posed a severe pressure on wild resources; researchers consequently sought to explore new sources, like cultivation, plant cell or organ culture, and chemical synthesis. Understanding biosynthesis of PTOX is one of the basic necessary steps for standard cultivation of medicinal plants and metabolite engineering. An important progress has been made in this field during the last two decades, particularly in the last ten years. Although a number of reviews concerning the related topic have existed, we specifically deal with biosynthesis of podophyllotoxin with an emphasis on the literatures of the past decade, highlighting characterization of genes encoding synthetic enzymes and down-stream metabolism of PTOX. The present review focuses on several key biosynthesis processes, important metabolites, function of related enzymes, and characterization of cDNA encoding the enzymes. Finally, the author proposed a hypothetical biosynthetic scheme of podophyllotoxin and perspectives.