Researchers hoping to mass produce a drug that combats resistant strains of malaria have genetically engineered a powerful new ally: a yeast that synthesizes a precursor to the antimalarial drug artemisinin. When the process is optimized and ramped up in 3 to 5 years, it could slash the price of artemisinin-based drugs, currently $8 to $15 per treatment course, by 10-fold, say the researchers.
Artemisinin is currently too expensive and rare for those who need it most: the poor in developing countries in Africa and Asia, where drug-resistant strains are now endemic. The bottleneck lies in limited harvests of the shrub from which the drug is extracted, Artemisia annua (sweet wormwood).
To bypass farming, University of California, Berkeley, chemical engineer Jay Keasling and colleagues decided to harness the synthetic powers of microorganisms. They previously reported partial success by tweaking natural biosynthetic processes and inserting a gene from A. annua into Escherichia coli, which is commonly used in industrial processes. But this only produced an intermediate compound that was several chemical steps short of artemisinic acid, the precursor they were aiming at.
For those last steps, they had to modify their previous process first so it would work in the yeast Saccharomyces cerevisiae. They then identified a novel enzyme at work in A. annua that completes the artemisinic acid synthesis and popped the gene for the enzyme into their yeast. Keasling says his team had assumed this enzyme would be just the first of three needed to create artemisinic acid. To their surprise, "this one enzyme did all three [steps]; it simplified our work significantly," he says. The team reports its results in the 13 April issue of Nature.
Anna Wang, spokesperson for the Medicines for Malaria Venture, a Geneva, Switzerland-based nonprofit, says her organization's scientists agree that "the science is genuinely fantastic." Unfortunately, practical use is a few years away. By then she expects to see other progress as well: greater harvests of the shrub, new techniques to squeeze more precursor, and alternative drugs. All of these approaches will have a role to play in fighting malaria, "so we hope they will all succeed," she says. The immediate challenge is reducing malaria's toll between now and then.