R&D News: MIT researchers engineer microbes for anticancer drug Taxol
According to MIT, the bacteria can produce 1,000 times more of the precursor, known as taxadiene, than any other engineered microbial strain.
Throughout human history, plants have been a source of potent medicines, including many cancer drugs discovered over the past few decades. However, it is quite difficult to discover such drugs and obtain them in large quantities from the plants or through chemical synthesis, said the researchers.
The technique, described in the October 1, 2010 issue of Science, could bring down the manufacturing costs of Taxol and also help scientists discover potential new drugs for cancer and other diseases such as hypertension and Alzheimer’s, said Gregory Stephanopoulos, who led the team of MIT and Tufts researchers and is one of the senior authors of the paper.
“If you can make Taxol a lot cheaper, that’s good, but what really gets people excited is the prospect of using our platform to discover other therapeutic compounds in an era of declining new pharmaceutical products and rapidly escalating costs for drug development,” said Stephanopoulos, the W.H. Dow Professor of Chemical Engineering at MIT.
Taxol, also known as paclitaxel, is a powerful cell-division inhibitor commonly used to treat ovarian, lung and breast cancers. It is also very expensive - about $10,000 per dose, although the cost of manufacturing that dose is only a few hundred dollars. (Patients usually receive one dose.)
Two to four Pacific yew trees are required to obtain enough Taxol to treat one patient, so in the 1990s, bioengineers came up with a way to produce it in the lab from cultured plant cells, or by extracting key intermediates from plant material like the needles of the decorative yew, said the researchers.
These methods generate enough material for patients, but do not produce sufficient quantities for synthesizing variants that may be far more potent for treating cancer and other diseases. Organic chemists have succeeded in synthesizing Taxol in the lab, but these methods involve 35 to 50 steps and have a very low yield, so they are not economical.
Also, they follow a different pathway than the plants, which makes it impossible to produce the pathway intermediates and change them to make new, potentially more powerful variations.
“By mimicking nature, we can now begin to produce these intermediates that the plant makes, so people can look at them and see if they have any therapeutic properties,” said Stephanopoulos. Moreover, they can synthesize variants of these intermediates that may have therapeutic properties for other diseases.
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