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Yeast, wormwood & bacterial genes combine in microbial factory to make antimalarial drug

day's biotechnology industry. There, protein drugs are produced primarily through fermentation by recombinant yeast that seldom have more than one gene inserted in them, perhaps with an additional piece of DNA fused to that gene to make the yeast spit out the protein.

Scientists have found it much harder to transplant entire gene systems to build new chemical assembly lines. Keasling, however, assembled 10 genes, including control elements, from three different organisms -- bacteria, yeast and wormwood-- and got them to work together successfully.

The goal of Keasling's group was to create bacteria capable of producing chemicals that can be used to make many kinds of isoprenoids, a class of some 30,000 known compounds of immense interest to the chemical and pharmaceutical industries. Isoprenoids are expensive to synthesize, however, and natural isoprenoids like taxol are costly to isolate from plant material. Often, too, these plants are rare and endangered, so that harvesting causes environmental damage.

Keasling's approach leapfrogs the bulk of the laborious synthesis necessary today, leaving only a few additional chemical alterations to obtain the desired drug or chemical. The development took more than three years and involved numerous people, primarily Keasling's UC Berkeley coauthors: post-doctoral fellows Vincent J. J. Martin and Jack D. Newman and graduate students Douglas J. Pitera and Sydnor T. Withers.

Other laboratories have tried to engineer the common intestinal bacteria, E. coli, to make isoprenoid precursors that could be used to produce drugs or industrial chemicals, but the methods involved hijacking the cell's own production factory. E. coli produce chemicals that can be used to make isoprenoid precursors, but diverting these chemicals to make more of them entails overcoming control mechanisms within the bacterial cell that are not fully understood.

Keasling's innovation was to leave E. coli's isoprenoid p
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Contact: Robert Sanders
rls@pa.urel.berkeley.edu
510-643-6998
University of California - Berkeley
1-Jun-2003


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