Synthetic biology can help extend anti-malaria drug eff...(2.6 million grant from the Bill and Meli...)

Date:3/6/2009

2.6 million grant from the Bill and Melinda Gates Foundation, through the Institute for OneWorld Health, a San Francisco-based nonprofit pharmaceutical company, to further develop his microbial artemisinin technology. A bio-tech start-up company, Amyris Biotechnologies, Inc., which is based in Emeryville, licensed the technology. In 2006, the collaboration reported the use of synthetic biology techniques to genetically engineer a strain of yeast (Saccharomyces cerevisiae) that was capable of producing high levels of artemisinic acid, the immediate precursor to artemisinin.

"Given the existence of known, relatively high-yielding chemistry for converting artemisinic acid to artemisinin or any other derivative that might be desired, microbial produced artemisinic acid is a viable source of this potent family of anti-malarial drugs," said Keasling when the yeast breakthrough was first announced.

The engineering of the yeast was a three-step process in which Keasling and his group first created a new metabolic pathway in the yeast, similar to the one created in E. coli, then introduced bacterial and wormwood genes into the yeast's DNA that interacted with the yeast's own genes to produce amorphadiene. Finally, they cloned the gene from the wormwood tree that produces the enzyme P450, which the plant uses to convert amorphadiene to artemisinic acid, and expressed it in the amorphadiene-producing yeast strain.

"We got it right the first time we tried it," Keasling said at his AAAS talk. "This is not unprecedented in the literature but it is really memorable when it happens to you!."

Last year, Keasling and his collaborators formed a new partnership with Sanofi-aventis, a leading pharmaceutical company based in France, with the goal of mass-producing low-cost microbial-based artemisinin by 2010.

"Over the long run, we expect to be able to reduce the production costs by an order of magnitude, which will fulfill our goal of meeti
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Contact: Lynn Yarris lcyarris@lbl.gov 510-486-5375 DOE/Lawrence Berkeley National Laboratory Source:Eurekalert

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