10 Emerging Technologies
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PHARMACEUTICALS Overhauling a microbe’s metabolism could yield a cheap malaria drug. By Erika Jonietz
In the valleys of central China, a fernlike weed called sweet wormwood grows in fields formerly dedicated to corn. The plant is the only source of artemisinin, a drug that is nearly 100 percent effective against malaria. But even with more farmers planting the crop, demand for artemisinin exceeds supply, driving its cost out of reach for many of the 500 million afflicted with malaria every year. University of California, Berkeley, bioengineer Jay Keasling aims to solve the supply problem – and reduce the cost of treatment to less than 25 cents – by mass-producing the compound in specially engineered bacteria.
Keasling’s efforts are an example of metabolic engineering, a field in which researchers try to optimize the complex processes whereby a cell produces or breaks down a particular substance. These processes rely on the step-by-step direction of genes; changing even one gene can alter the outcome. Most metabolic engineering has previously focused on modifying a cell’s natural processes by inserting, mutating, or deleting a few key genes. According to James Collins, a biological engineer at Boston University, “what Jay is doing is a bit more radical”: creating entirely new metabolic pathways by integrating multiple genes from different organisms into a host microbe.
Keasling began his artemisinin project by inserting a set of yeast genes into the common bacterium E. coli. These genes induce the bacterium to make the chemical precursor to terpenes – the family of compounds to which artemisinin belongs. Adding in another two genes causes the bacterium to make a specific artemisinin precursor. Introducing a few more genes from sweet wormwood should get the microbe to make artemisinic acid, which is one simple chemical step away from artemisinin. But since E. coli don’t normally produce these chemicals, each step of the process will have to be carefully contrived and optimized. “There’s a lot of engineering still,” says Keasling.
A $42.6 million grant from the Bill and Melinda Gates Foundation should help. In December, the foundation awarded the money to Keasling, his Emeryville, CA, startup Amyris Biotechnologies, and San Francisco’s Institute for OneWorld Health, a nonprofit that aims to secure U.S. Food and Drug Administration approval for bacteria-derived artemisinin within five years.
The promise of bacterial factories doesn’t end with artemisinin. Amyris Biotechnologies hopes to adapt Keasling’s terpene precursor pathway to make prostratin, a promising anti-HIV compound found in the bark of the mamala tree on Samoa. With different alterations to the pathway, bacteria could make paclitaxel, the breast cancer drug sold under the brand Taxol and now isolated from yew trees.
Ultimately, Keasling believes, new technologies for analyzing and understanding cellular pathways will enable researchers to engineer microbes to produce a huge range of chemicals, from drugs to plastics. And unlike conventional chemical engineering, bacteria do their job cleanly, without requiring or producing environmentally harmful compounds. “We’ve got all these great tools,” Keasling says. “Now we can start to put these to use to solve this one particular problem: how to engineer a cell to do the kinds of chemistries that you want it to do.”