Researchers from Tufts and Massachusetts Institute of Technology (MIT) have come one step closer to making strides against cancer with the recent discovery of a more efficient and cost-effective method of producing taxadiene, the precursor to the anti-cancer drug Taxol.
Taxol, also known as Paclitaxel, has powerful medicinal properties and is used as a treatment for many types of cancers, including lung, ovarian and breast cancers, according to Blaine Pfeifer, the lead researcher on the project and an assistant professor of Chemical and Biological Engineering at Tufts.
The new technique, which creates the molecule taxadiene using E. coli bacteria, allows scientists to produce 1,000 times more of the molecule than previous engineered microbial techniques.
Researchers published the results of the project in the Oct. 1 issue of the journal Science.
Taxadiene was originally procured from the bark of the yew tree, but this technique was inefficient, according to Greg Stephanopoulos, a professor of Chemical Engineering and Biotechnology at MIT, who led the team of project researchers.
"It was inefficient because two to four fully grown trees of [the] age of 100 years had to be destroyed in order to extract enough materials for the treatment of one patient," he said.
The 1990s saw progress as bioengineers resorted to extracting molecules from the needles of the decorative yew instead of relying on fully grown trees to produce Taxol, according to Stephanopoulos.
The overall yield, however, was nevertheless modest and uneconomical. Researchers therefore became interested in the possibility of synthesizing Taxol through a procedure that was free of plant biology, according to Pfeifer.
Stephanopoulos noted that the solution was discovered within E. coli bacteria found in the intestinal tracts of warm-blooded organisms.
The scientific procedure involves retrieving a cell from the yew tree and transplanting it into E. coli via molecular biological methods, Pfeifer said.
E. coli was chosen as the principal agent in this project, which relied on chemical engineering, because of its simple structure, according to Pfeifer.
"E. coli grows much more frequently, is easy to manipulate and is engineering-friendly," Pfeifer said.
The success the project achieved was groundbreaking, according to Yong Wang, a professor at East China University of Science and Technology, who contributed to the research.
"To get this kind of complex compound [Taxol] from E. coli without introducing additional pathways for precursor supply is unprecedented," Wang told the Daily in an e-mail.
Even though the taxadiene discovery presents just one step in Taxol production, Pfeifer views the project as a stepping stone for further advancements in the production of the anti-cancer agent.
"With this success, we hope that similar engineering can be done to reach the final compound," Pfeifer said. "There's hope that there must be a more cost-effective, resource-effective route towards Taxol."
"We are also hopeful that we could make new derivatives of Taxol by manipulating the pathways to produce better anti-cancer drugs," Pfeifer added.
Some of the noteworthy challenges to the project were molecular biological in nature, like the obstacle of bottlenecks, which arise when a lack of enzymes slows molecular synthesis, according to Stephanopoulos.
"When bottleneck is overcome, then that allows the microorganism to synthesize the molecule at a much higher rate," Stephanopoulos said.
National Institutes of Health, a federal organization that provides financial support for biomedical research, was one of the critical sources of funding for the project, which lasted about three years, according to Stephanopoulos.
