Cloned Gene Leads to Faster-Growing Anticancer Enzyme
By Merritt McKinney
WESTPORT, Jan 28 (Reuters Health) - Scientists have cloned and sequenced an enzyme called epothilone that has anticancer properties, according to a report in the January 28th issue of Science.
By inserting the epothilone gene into a bacterium that produces the enzyme much more quickly than its natural host, researchers have taken the first step towards producing enough epothilone for clinical trials.
Epothilones have been considered a possible alternative to the drug paclitaxel, since they act against cancer in much the same way, according to Dr. Li Tang and colleagues at KOSAN Biosciences in Hayward, California. The enzymes have certain advantages over paclitaxel "...in that they are effective against Taxol-resistant tumors and are sufficiently water soluble that they do not require deleterious solubilizing additives," the authors write.
However, the natural host of epothilones, Sorangium cellulosum, produces the enzymes slowly and in small quantities, making the production of epothilone-based therapy economically unfeasible, according to the report.
In the current research, Dr. Tang's team successfully cloned the epothilone gene and transferred it to the bacterium Streptomyces coelicolor. This bacterium produced epothilone 10 times faster than its natural host does. In addition, while little is known about the genetics of S. cellulosum, S. coelicolor is easy to manipulate genetically, the researchers note.
"Given the high growth rate and pliability of S. coelicolor to genetic and conventional strain improvement, this system promises to evolve into the preferred producer of epothilone," the authors write. "[I]t should now be possible to construct an expression system for the currently most attractive clinical candidate, desoxyepothilone, as the sole fermentation product."
In an interview with Reuters Health, Dr. Daniel V. Santi, the chief executive officer of KOSAN, said that the company hopes to produce enough of the enzyme to begin clinical trials within the next year or two. He noted that animal tests conducted by other teams have produced promising results.