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The Blog of Drug Discovery News

MIT is putting nature to work for pharma

All right, nature, get to work! You’re on academia’s clock now, and pharma’s in the future

That’s right, the Massachusetts Institute of Technology (MIT) in Cambridge, Mass., is appropriating some of Mother Nature’s children and putting them to work to produce drugs, finding ways to make at least one plant (periwinkle) and at least one microbe (E. coli) make oncology drugs, according to a pair of fall announcements.

The first announcement came in late September with word that MIT researchers and collaborators from Tufts University have now engineered E. coli bacteria to produce large quantities of a critical compound that is a precursor to the cancer drug Taxol, originally isolated from the bark of the Pacific yew tree. The tree’s bacteria can produce 1,000 times more of the precursor, known as taxadiene, than any other engineered microbial strain, and the new MIT technique could bring down the manufacturing costs of Taxol.

More than that, it could also help researchers discover potential new drugs for cancer and other diseases such as hypertension and Alzheimer’s, says Gregory Stephanopoulos, who led the team of MIT and Tufts researchers.

“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,” says Stephanopoulos, the W.H. Dow Professor of Chemical Engineering at MIT.

Early November brought the second announcement, that researchers led by an MIT associate professor, Sarah O’Connor, have added bacterial genes to the periwinkle plant, enabling it to attach halogens such as chlorine or bromine to a class of compounds called alkaloids that the plant normally produces. Many alkaloids have pharmaceutical properties, and halogens, which are often added to antibiotics and other drugs, can make medicines more effective or last longer in the body, MIT reports.

The team’s primary target, an alkaloid called vinblastine, is commonly used to treat cancers such as Hodgkin’s lymphoma. O’Connor sees vinblastine and other drugs made by plants as scaffolds that she can modify in a variety of ways to enhance their effectiveness.

“We’re trying to use plant biosynthetic mechanisms to easily make a whole range of different iterations of natural products,” she says. “If you tweak the structure of natural products, very often you get different or improved biological and pharmacological activity.”

Although engineering new genes into plants is nothing new, O’Connor’s approach, known as metabolic engineering, goes beyond simply adding a gene that codes for a novel protein. As MIT described it, “Metabolic engineers tinker with the series of reactions that the host organisms use to build new molecules, adding genes for new enzymes that reshape these natural synthetic pathways. This can lead to a huge variety of end products.”

In future work, the researchers hope to engineer full periwinkle plants to produce the novel compounds. They are also working on improving the overall yield of the synthesis, which is about 15-fold lower than the plant’s yield of naturally occurring alkaloids.

With this much activity in two such disparate organisms, one can only imagine what MIT will put into service next. Maybe they can recruit some of those weeds in my garden to work for pharma so that they can do something more productive than rip my hands to shreds as I yank them up.

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November 4, 2010 - Posted by | Academia & Non-Profit, Labwork & Science | , , ,

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