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Now MIT chemists have found a new way to
expand plants’ pharmaceutical repertoire by genetically engineering
them to produce unnatural variants of their usual products.
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.
The periwinkle plant, also known as Catharanthus roseus,
produces several compounds with medicinal properties,
the anticancer drug vinblastine.
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.
O’Connor, graduate student Weerawat Runguphan and former postdoctoral associate Xudong Qu describe their engineered periwinkle plants in the Nov. 3 online edition of Nature.
The research was funded by the
National Institutes of Health and the American Cancer Society.
However, O’Connor’s approach, known as metabolic engineering, goes beyond simply adding a gene that codes for a novel protein. 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
Though humans have long recognized the value of medicinal plants,
On the other hand, the complexity of plant synthetic pathways means that in many cases, it may be easier to modify the plant rather than try to reconstitute the entire plant pathway in a different organism such as bacteria.
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.
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.
One way to do that is to introduce the
halogen further along in the process, said O’Connor.