Podophyllotoxin: Current approaches to its biotechnological production and future challenges

Many plant-derived agents are being used to treat cancer, including taxol, vinblastine, vincristine, or camptothecin and podophyllotoxin derivatives, among others. Plant biotechnology can provide a new tool for the production of anticancer agents but in spite of considerable efforts to produce vinblastine and vincristine in cell cultures and knowledge of the biosynthetic pathway of Catharanthus roseus alkaloids, the biotechnological production of taxol has only been achieved at an industrial level by companies such as Phyton Biotech and Cytoclonal Pharmaceutics. Podophyllotoxin was isolated as the active antitumor agent from the roots of Podophyllum species and more recently from the genus Linum and others. Etoposide, teniposide, and etophos are semi-synthetic derivatives of podophyllotoxin and are used in the treatment of cancer. Biotechnological approaches, including the use of cell cultures, biotransformation, or metabolic engineering techniques to manipulate the biosynthetic pathway, represent an alternative for the production of podophyllotoxin and are discussed in this review.