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In a deft act of genomic manipulation, researchers at the J. Craig Venter Institute, in Rockville, MD, transplanted a bacterial genome into yeast, altered it, and then transplanted it back into a hollowed bacterial shell, producing a viable new microbe. The technique may provide a way to more easily genetically engineer organisms not commonly studied in the lab and could aid in the expanding effort to create microbes that can produce fuels or clean up toxic chemicals. “This research enhances our capabilities in genome engineering and opens new applications,” says Jim Collins, a bioengineer at Boston University, who was not involved in the research. “I see this as an important advance relevant to the bioenergy and biomaterials industries.”

Thanks to decades of scientific research, microbes such as yeast and E. coli come with an arsenal of genetic tools that have enabled researchers to enact genetic overhauls of increasing complexity–replacing entire chemical pathways, for example, to make microbes that can perform more complex tasks or produce materials more efficiently. But many microbes of industrial interest, such as those with unique capabilities for generating chemicals, aren’t as easily hackable. Target organisms include photosynthetic microbes, which scientists hope can be engineered to efficiently turn light into fuel. By inserting the genomes of these bacteria into yeast, the researchers at the Venter Institute are more easily able to engineer them. “People want the capability of yeast or E. coli but want to have the photosynthetic apparatus there,” says David Berry, a partner at Flagship Ventures and the 2007 TR35 innovator of the year. “Combining those two genomes would be interesting in the biofuels world.”

The new technology emerged from the Venter Institute’s high-profile quest to create life from scratch–generating a synthetic genome and then using it to control, or reboot, a recipient cell. In 2007, Venter researchers published a paper describing a genome transplant, in which a genome from one type of bacteria was transferred to a closely related one, giving the host the characteristics of its donor. Then, last year, the researchers created a synthetic genome by stitching together pieces of synthesized DNA.

To build a synthetic organism, however, researchers will have to transplant that synthetic genome into a cell and have it successfully reboot the cell. But that last step has proved problematic. The synthetic genome was assembled in yeast, which means it lacked some of the molecular markings characteristic of bacteria. Researchers discovered that without those markings, the host bacterium viewed the transplanted genome as a foreign invader and destroyed it.

The new technique, published online in the journal Science, provides a way around that hurdle. Sanjay Vashee and colleagues first transplanted the genome of Mycoplasma mycoides into yeast. While scientists had previously grown pieces of bacterial DNA in yeast, this is the first instance of growing an entire bacterial genome this way. Using existing tools for genetically engineering yeast, researchers then chemically altered the bacterial genetic material so that it carried the molecular markings characteristic of bacteria. They transplanted the modified genome into Mycoplasma capricolum, a species closely related to the mycoides genome donor, to create a viable mycoides cell.

The researchers now aim to test the technique on other bacteria. “We want to start transferring this technology to organisms that are more relevant industrially or for biofuels,” says Vashee. For example, he says, genetic pathways from organisms that can break down environmental pollutants could be engineered into bacteria that could survive in harsh and contaminated environments, such as acidic ponds, and then used to clean up those areas.

The technology will likely find its way to Synthetic Genomics, a biofuels start-up founded by Venter that is developing genetically modified algae to produce fuels and other chemicals. The company announced a $300 million partnership with ExxonMobil last month.

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Credit: Courtesy J. Craig Venter Institute

Tagged: Biomedicine, biofuels, genetic engineering, Craig Venter, Synthetic Genomics

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