Engineers build mini drug-producing biofactories in yeast

August 15, 2008,

Researchers at the California Institute of Technology have developed a novel way to churn out large quantities of drugs, including antiplaque toothpaste additives, antibiotics, nicotine, and even morphine, using mini biofactories--in yeast.

A paper describing the research, now available online, will be featured as the cover article of the September issue of Nature Chemical Biology.

Christina D. Smolke, an assistant professor of chemical engineering at Caltech, along with graduate student Kristy Hawkins, genetically modified common baker's yeast (Saccharomyces cerevisiae) 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 antispasmodic effects, pain relief, and hair growth acceleration. Other BIAs have shown anticancer, antioxidant, antimalarial, and anti-HIV potential.

"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," says Smolke, whose lab focuses on using biology as a technology for the synthesis of new chemicals, materials, and products. 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 antiplaque 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. "But even the intermediate molecules that we are producing can exhibit important and valuable activities, and a related area of research will be to examine more closely the pharmacological activities of these metabolites and derivatives now that pure sources can be obtained," says Smolke, who estimates that her system could be used for the large-scale manufacture of BIA compounds in one to three years.

Smolke and Hawkins also plan to extend their research to the production of BIAs that don't normally exist in nature.

"If one thinks of these molecules as encoding functions that are of interest to us, the ability to produce nonnatural alkaloids will provide access to more diverse functions and activities. By expanding to nonnatural alkaloids, we can search for molecules that provide enhanced activities, new activities, and not be limited by the activities that have been selected for in nature," says Smolke.

"Our work has the potential to result in new therapeutic drugs for a broad range of diseases. This work also provides an exciting example of the increased complexity with which we are engineering biological systems to address global societal challenges," she says.

Source: California Institute of Technology

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5 / 5 (1) Aug 15, 2008
What happens if the yeast escapes and enters the food chain?

I prefer the use of single celled GM organisms to complex multicellular ones but I think -precautions still need to be made to ensure the yeast is not viable in the wild.
1 / 5 (1) Aug 15, 2008
What if it get into a bakery? Your bread might have morphine in it by accident.
not rated yet Aug 16, 2008
all life on this planet struggles for existance, if a GM lifeform gets released into the wild, it is at a distinct disadvantage to natural lifeforms because so much of its genome has been redirected to meet our needs.
not rated yet Aug 16, 2008
The ultimate goal is to clone the genes needed to produce LSD, psilocybin, THC, DMT and others into common pests and then spread them around the globe to allow everyone the freedom of choice.

Unlimited access to drugs should end that moronic war on drugs so that all the money now happily appropriated by a band of useless parasites can be spent on drug research and education.

Substances like LSD offer everyone a chance of becoming a better human being - more aware of themselves, with better understanding of reality and most importantly with much more control over their lives then standard social imprinting which we all undergo during growing up allows.

I consider banning LSD and related compounds one of the worst crimes against humanity ever committed.
not rated yet Apr 20, 2009
There are cases of gm plants (corn I think) that has moved into the DNA of it's indiginous predecessor by cross-crop biotic pollination, carrying unwanted genetic characteristics. I think it was Journal of Science several years ago and something to do with indigenous Mexican corn.

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