Gates foundation to promote synthetic biology

Most people associate E. coli with bad chicken, but researchers say the microbe can be used to produce new drugs.

The emerging field of synthetic biology--creating organisms in the lab that act like those found in nature--received a big boost Monday in the form of a $42.5 million grant from the Bill & Melinda Gates Foundation.

The grant--which will be shared by the University of California at Berkeley, the Institute for OneWorld Health, and Albany, Calif.-based upstart Amyris Biotechnologies--will help refine a process for producing the antimalarial drug artemisinin in the lab with genetically engineered microbes.

But that's just the start. Research on the project, ideally, will allow Amyris and others to create several types of new medicines with the molecular foundation, or precursor, used in synthetic artemisinin.

"What we've done is engineer this strain (of microbes) that can make copious amounts of precursors. We now have a firehose of precursors," said Jack Newman, founding scientist of Amyris. "They very same pathways can be used for anticancer (drugs), antivirals, antioxidants."

Others, such as Nobel Prize winner Steven Chu, have speculated that synthetic biological techniques can be used to create fuel. Start-up Cambrios Technologies, meanwhile, is using genetically modified microbes to produce compounds that could become exploited by the electronics industry.

Jay Keasling, a UC Berkeley professor and a pioneer in the synthetic-biology field, says these techniques can also be used in toxic cleanup or to neutralize poisons such as sarin. A paper coming out this December will describe an organism that can harvest radioactive material.

"Microbes excel at producing complicated molecules," Keasling said.

Synthetic biology involves taking a metabolic pathway found in nature and grafting it into the genetic code of a microbe like yeast or, as in the case of artemisinin, E. coli. While most people think of E. coli as harmful, molecular biologists call it the workhorse of their field, because its genetic sequence is well-understood and new generations can be produced in a half-hour.

The production process is not synthetic because the resulting compound is still produced through biological means. The term synthetic comes from the fact that the compound comes out of an organism with a genetic code that isn't ordinarily found in nature. While some companies have already released products that were produced in this manner, the resulting molecules are relatively small.

If successful, these processes could substantially change the pharmaceutical industry. Artemisinin is produced by a wormwood plant that naturally grows in Southeast Asian mangrove swamps. It's one of the most effective drugs for the disease, and it's not cheap. Providing it to 70 percent of the malaria victims in Africa would cost about $1 billion, according to various statistics.

"You would need to plant the state of Rhode Island to meet demand," said Newman, adding that the plants take about six months to mature.

Artificially produced artemisinin should cost about half as much. Additionally, batches of the drug are more consistent. Production of the drug would not be subject to political instability or deforestation, a problem in tropical nations, from which many of the latest drugs come.

The three organizations will use the grant money to further refine the drug for production. Keasling will conduct research and development, the Institute for OneWorld Health will try to clear the regulatory hurdles, and Amyris will concentrate on production. For this project, UC Berkeley is issuing royalty-free licenses on its technology to the insitute, and Amyris will produce the drug at costs.

Right now, only an intermediate form of synthetic artemisinin has been produced. It could be used to combat malaria, but it would still be costly. One of the next major projects will involve identifying a gene to produce it cheaply.

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