August 20, 2008

‘Biofactories’ Can Produce More Drugs

By From staff reports

Caltech researchers have developed a novel way to churn out large quantities of drugs, including anti-plaque toothpaste additives, antibiotics, nicotine, and even morphine, using mini "biofactories" in yeast.

Christina D. Smolke, an assistant professor of chemical engineering at Caltech, along with graduate student Kristy Hawkins, genetically modified common baker's yeast so that it contained the genes for several plant enzymes.

The enzymes allow the yeast to produce a chemical called reticuline, which is a precursor for many different classes of benzylisoquinoline alkaloid (BIA) molecules.

The BIA molecules are a large group of chemically intricate compounds, such as morphine, nicotine, and codeine, which are naturally produced by plants.

BIA molecules exhibit a wide variety of pharmacological activities, including anti-spasmodic effects, pain relief, and hair growth acceleration. Other BIAs have shown anti-cancer, antioxidant, anti-malarial, and anti-HIV potential, Caltech officials said.

"There are estimated to be thousands of members in the BIA family, and having a source for obtaining large quantities of specific BIA molecules is critical to gaining access to the diverse functional activities provided by these molecules," Smolke said.

However, the natural plant sources of BIAs accumulate only a small number of the molecules, usually "end products" like morphine and codeine that, while valuable, can't be turned into other compounds, thus limiting the availability of useful new products.

To their reticuline-producing yeast, Smolke and Hawkins added the genes for other enzymes, from both plants and humans, which allowed the yeast to efficiently generate large quantities of the precursors for sanguinarine, a toothpaste additive with anti-plaque properties; berberine, an antibiotic; and morphine.

The researchers are now in the process of engineering their yeast so that they will turn these precursor molecules into the final, pharmacologically useful molecules.

Smolke estimates that her system could be used for the large- scale manufacture of BIA compounds in one to three years.

"Our work has the potential to result in new therapeutic drugs for a broad range of diseases," she said.


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