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MIT chemists engineer plants to produce new drugs
Date:11/3/2010

enzymes that reshape these natural synthetic pathways. This can lead to a huge variety of end products.

Most metabolic engineers use bacteria as their host organism, in part because their genes are easier to manipulate. O'Connor's work with plants makes her a rare exception. She doesn't believe one approach is better than the other, but one factor that drew her to engineer plants is that most plant synthetic pathways have not been completely revealed. "You can't reconstitute a whole plant pathway in bacteria unless you have all the genes," she said.

In previous experiments, O'Connor and her students induced periwinkle root cells to create novel compounds by feeding them slightly altered versions of their usual starting materials. In the new study, they engineered the cells to express genes that code for enzymes that attach chlorine or bromine to vinblastine precursors and other alkaloids.

The two new genes came from bacteria that naturally produce halogenated compounds. It's much more rare for plants to generate such compounds on their own, said O'Connor. It is also possible, though very difficult, to synthesize halogenated alkaloids in a laboratory.

To make alkaloids, plants first convert an amino acid called tryptophan into tryptamine. After that initial step, about a dozen more reactions are required, and the plants can produce hundreds of different final products. In the new genetically engineered plants, a bacterial enzyme called halogenase attaches a chlorine (or bromine) atom to tryptamine. That halogen stays on the molecule throughout the synthesis.

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. One way to do that is to introduce the halogen further along in the process, said O'Connor.


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Contact: Jennifer Hirsch
jfhirsch@mit.edu
617-253-1682
Massachusetts Institute of Technology
Source:Eurekalert

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