Yeast is not often associated with efforts to control a global health problem, but work published on page 940 of this issue manages to bridge the gap. Jay Keasling, a synthetic chemist at the University of California, Berkeley, and his team have engineered yeast cells to produce an important precursor for a drug to treat malaria.

Artemisinin is an extremely effective treatment for malaria, but is also very expensive and in short supply. Normally extracted from sweet wormwood (Artemisia annua), the active compound has proved remarkably difficult to synthesize in the laboratory.

Keasling and his team already had ample experience of modifying microbes to produce or degrade specific compounds when they turned their attention to the biosynthesis of artemisinin. In 2000, the enzyme responsible for the first step in the production of the drug in plants was discovered. Three years later Keasling's team showed that this enzyme could be introduced into microbes, which could then carry out the first steps of the synthesis, albeit with low efficiency.

Soon after this advance, Keasling teamed up with the Institute for OneWorld Health, a non-profit drug company based in San Francisco, and Amyris Biotechnologies of Emeryville, California, to try to complete the synthesis with funding from the Bill & Melinda Gates Foundation. The partners divided the work up: Keasling tackled the synthesis, Amyris was charged with scaling the process up, and OneWorld Health took on responsibility for regulatory work to prove that the compound being produced was equivalent to the natural form.

Keasling opted to use brewer's yeast (Saccharomyces cerevisiae) for his putative microbial factory because “it is well studied and plant enzymes seem to be more functional in yeast”, he says. The product he was aiming for was artemisinic acid, which can readily be converted into artemisinin. One element of the biosynthetic pathway already existed in yeast, so the first task was to mutate certain genes to maximize production for this step. Next the team repeated its earlier work and introduced the plant enzyme into the yeast. Finally, the group needed to find a gene that would perform the final conversion of intermediates to artemisinic acid — a three-step reaction. The researchers found what they were looking for after cloning and testing a number of potential candidates. “It was very helpful that one enzyme catalysed all three reactions we needed,” Keasling says.

“Going into the project, it was a significant challenge but I am actually surprised at how well every step worked,” says Keasling. Indeed, an added bonus was that yeast seems to transport the artemisinic acid out of the cell, making isolation and collection of the product much easier.

Although the pathway still requires optimization, Keasling remains optimistic that this can be achieved. “We have a real opportunity to get this treatment to people who need it,” he says. According to his estimates, the drug could be offered at a fraction of current costs.