Cellular Chemical Factory Lowers Cost of Malaria Treatment

The Bill & Melinda Gates Foundation has awarded a $42.6-milliongrant to collaborators from OneWorld Health (San Francisco, CA, www.oneworldhealth.org),University of California, Berkeley (UC Berkeley, Berkeley, CA, www.berkeley.edu), and AmyrisBiotechnologies, Inc. (East Bay, CA, www.amyrisbiotech.com) for thedevelopment of affordable antimalarial drugs.

    To produce the drug's key ingredient, artemisinin,the team uses a synthetic biological process pioneered by Jay D.Keasling, PhD, UC Berkeley professor of chemical engineering andbioengineering.  Researchers insert genes from yeast and thewormwood plant—the source of the artemisinin—into E. coli bacteria. The new pathwaymakes the organism produce artemisinin quickly and efficiently. Themicrobes are grown in large fermentors and formulated as an oral orsuppository drug. "We can produce enough of the product without havingto chop down a whole forest to get a single dose," says Jack D. Newman,PhD, founding scientist at Amyris. Typical methods of extractingartemisinin from the plant are labor intensive, expensive to produce,and may retain toxic impurities in the final drug product. Whereas thecost of treatments produced by conventional processes is $2.40 perdose, the Amyris–UC Berkeley drug will cost approximately $0.21.

     In addition, the process is more environmentallyfriendly than typical synthetic chemistry methods, which produce toxicwaste products. "Our technique is organic and biodegradable, which meansthat you don't have to worry about storage and discharge," he explains."And, there's costs associated with process chemistry. A lot of processchemists must consider how they're going to recycle their solvents whenthey develop their processes."

    To make the process suitable for industrialproduction, Amyris will partner with large-scale manufacturers toproduce the several hundred tons of artemisinin that the World HealthOrganization estimates are needed annually. "We are working to come upwith a set of standard operating procedures that we can hand off to alarge-scale manufacturer," says Newman. In addition, the team alsoplans to apply the method to other types of drugs developed withnatural products. "The process is applicable to the entire class ofisoprenoids, which form the basis of many pharmaceuticals," saysNewman. Potential applications could include taxol, an anticancer drugmade with a product of the Pacific yew tree, and an anti-AIDS drug madewith a native Samoan mamala tree extract.

–Kaylynn Chiarello