Tobacco Engineered to Produce Anti-Cancer Drug—Crops as Drug Production Systems

Tobacco plants in the laboratory. Our extensive knowledge of tobacco genetics allows us to use them to produce plant-derived therapeutics.
Tobacco plants in the laboratory. Our extensive knowledge of tobacco genetics allows us to use them to produce plant-derived therapeutics.
A paper published in Science this week describes use of engineered tobacco plants to produce a precursor of etoposide, a key anti-cancer drug. The paper illustrates how engineered crops could be used for production of drugs or other compounds that are difficult to isolate or purify from natural sources.

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.

Cell-Free Expression: Non-Radioactive Detection/Applications

The Transcend™ Non-Radioactive Translation Detection Systems allow nonradioactive detection of proteins synthesized using cell free expression. Using these systems, biotinylated lysine residues are incorporated into nascent proteins during translation, This biotinylated lysine is added to the translation reaction as a precharged ε-labeled biotinylated lysine-tRNA complex rather than a free amino acid. After SDS-PAGE and electroblotting, the biotinylated proteins can be visualized by binding either Streptavidin-Alkaline Phosphatase (Streptavidin-AP) or Streptavidin-Horseradish Peroxidase (Streptavidin-HRP), followed either by colorimetric or chemiluminescent detection. Typically, these methods can detect 0.5–5ng of protein within 3–4 hours after gel electrophoresis and can be used for a variety of proteomics related applications. Examples include: Continue reading “Cell-Free Expression: Non-Radioactive Detection/Applications”