Although etoposide is derived from a plant compound, little is known about its natural biosynthetic pathway. The authors of the paper first used genome mining to identify candidate genes that may be involved in synthesis of the etoposide precursor in its native host—the rare and slow-growing mayapple plant. Through a complex process of elimination, were eventually able to identify 10 enzymes involved in biosynthesis, and reconstitute the pathway in engineered tobacco plants.
The paper showcases some elegant scientific detective work, making use of both genomic analysis and classical genetic engineering to solve the puzzle of etoposide biosynthesis. The results presented also illustrate the potential benefit of engineering agricultural crops to be used as drug production systems, and generate hope for a much more abundant, easily cultivable supply of these and other therapeutic compounds.
The use of tobacco to generate an anti-cancer compound. Delightful science.
Here’s the Science Story
And the Paper
Lau, W. and Sattely, E.S. (2015) Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone Science 349, 1224–1228.