Genetically Engineered Periwinkle Plants Produce Anticancer Drugs

By transplanting bacterial genes, drug developers have genetically engineered Madagascar periwinkle (Catharanthus) plants to produce halogenated variants of the natural anticancer drug vinblastine.

The periwinkle plant is used by herbalists as an astringent. As a source of natural drugs, its primary use has been to help treat menstrual periods where there was too much heavy bleeding. It has also been used to treat urinary tract problems, such as hematuria, or blood in the urine. Periwinkle also has been used to treat colitis and diarrhea, plus other types of digestive problems, which involve bleeding.

Vinblastine is one the most effective treatments for Hodgkin's disease, and is typically used in combination with doxorubicin, bleomycin, and dacarbazine. It is also used to treat non-Hodgkin's lymphomas, mycosis fungoides, and Letterer-Siwe disease. Vinblastine is also used to treat cancer of the testis in combination with other cancer drugs, and Kaposi's sarcoma alone, or in combination with other drugs. Vinblastine is also used less frequently to treat other types of cancer.

Vinblastine acts by preventing the formation of microtubules in cells. As microtubules are required for cell division, disruption of this function inhibits cell replication, including the replication the cancer cells.

A paper published in the November 3, 2010, online edition of the journal Nature described how investigators at the Massachusetts Institute of Technology (MIT; Cambridge, USA) added bacterial genes to the periwinkle plant, enabling it to attach halogens such as chlorine or bromine to alkaloids such as vinblastine. The halogenases encoded by the bacterial genes functioned within the context of the plant cell to generate chlorinated tryptophan, which was then shuttled into monoterpene indole alkaloid metabolism to yield chlorinated alkaloids.

"We are trying to use plant biosynthetic mechanisms to easily make a whole range of different iterations of natural products,” said senior author Dr. Sarah O'Connor, associate professor of chemistry at the Massachusetts Institute of Technology. "If you tweak the structure of natural products, very often you get different or improved biological and pharmacological activity. Medicinal plants, despite their genetic and developmental complexity, therefore seem to be a viable platform for synthetic biology efforts.”

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