Microbes can be resistant to genetic engineering. There's simply not enough DNA in some of them to permit significant alteration. But by building a bacterial genome inside yeast—a more complex and information-rich eukaryote that is one of mankind's oldest genetic engineering projects—scientists have successfully created new, synthetic bacterial strains, according to a paper published today in Science.

Carole Lartigue and colleagues at the J. Craig Venter Institute have been seeking to build living cells from scratch. The ultimate goal is to produce man-made microbes to solve man-made problems, whether eating up carbon dioxide or making the fuels of the future.

Working with microbes Mycoplasma mycoides and Mycoplasma capricolum (goat pathogens with extremely small genetic blueprints), the scientists previously swapped one genome for the other. And colleagues at JCVI chemically synthesized the genome of Mycoplasma genitalium inside yeast.

Now Lartigue and colleagues report success in synthesizing, cloning and transplanting a M. mycoides genome into M. capricolum cells. The key? Yeast again.

By working inside the roomier (and better scientifically understood) confines of yeast, the researchers can more easily manipulate the synthetic genetic material. This enabled them to clone the Mycoplasma genome inside the yeast one and to build in protections for this synthetic genome from inherent mechanisms that protect cells from foreign DNA—akin to the human immune system rejecting a transplanted organ.

Once transplanted back from the yeast, specially tagged M. mycoides genomes began to appear in the subsequent cells divided from the host M. capricolum, proving they had been accepted by the host. This opens the door to broad tinkering with genomes in yeast by providing a method to get them back into host cells—one step closer to a fully synthetic life form.

Yeast Image: Courtesy of Lawrence Berkeley National Laboratory