Research progress in biosynthesis of podophyllotoxin and its derivatives / 生物工程学报

Podophyllotoxin (PTOX) is an aryl-tetralin lignan of plant origin found in some species of Podophyllum such as Dysosma versipellis, Diphylleia sinensis, and Sinopodophyllum hexandrum. Etoposide and teniposide are produced semisynthetically from PTOX and used clinically to treat several forms of cancer. As a typical representative of new drug discovery from natural products, the production of PTOX solely depends on extraction from plants, resulting in severe contradiction between supply and demand. With the advantages of unconstrained resources and eco-friendly reaction conditions, biosynthesis method has become a trend in the production of PTOX and its derivatives. In this review, we summarize the research progress of PTOX biosynthesis in plants and expound the functions of the key enzymes as well as their subcellular location. The synthetic biology for production of PTOX intermediates in a tobacco chassis is also introduced. Finally, the heterologous expression and biotransformation of PTOX in microorganisms is summarized, which sets the foundation for the efficient microbial production of PTOX using cell factories.

Effect of elicitors on the enhancement of podophyllotoxin biosynthesis in suspension cultures of linum album

The possibility of enhancment accumulation of podophyllotoxin [PTOX] has been studied in cultures of cell suspension of Linum album Kotschy ex Boiss. [Linaceae] producing PTOX was studied. Attempts were made to manipulate the biosynthetic pathway of PTOX by some biotic [yeast extract] and abiotic [Ag[+], Pb[2+] and Cd[2+]] elicitors for 24 or 48 hr in Murashige and Skoog [MS] medium. Silver significantly enhanced PTOX production up to 0.24% [mg/g cell dry wt.] in cultures. This effect could be attributed to the inhibitory role of silver on production of ethylene