building better bacteria

The Scientist | Researchers from the J. Craig Venter Institute have developed a technique for generating modified strains of bacteria with novel, genetically engineered properties, they report online today (August 20) in Science. The advance could help scientists tweak microorganisms to more efficiently produce biofuels, the researchers say.

"I think it's an important and interesting advance," said James Collins, a bioengineer at Boston University who was not involved in the study. "I suspect this will turn out to be quite important for bioengineering and bioenergy systems."

Last year, Venter, an author on the paper (and a member of The Scientist's editorial board), reported that he and his collaborators had created a synthetic bacterial genome and cloned it into a yeast cell. However, they were unable to transfer the genome into a cell that would use the genetic code to produce a functioning version of the organism. In the current paper, the researchers present a technique for doing just that.

The Venter team first cloned the genome of the bacterium Mycoplasma mycoides into a yeast cell. They then altered the genome, using the myriad tools available for yeast gene manipulation. In the procedure's trickiest step, they transplanted the yeast-bound bacterial genome into a closely related bacterium, Mycoplasma capricolum, coaxing it to "take this bacterial genome and boot it up" and generate their mutant strain, said Sanjay Vashee, a synthetic biologist at the institute and the corresponding author on the paper.

The hurdle Vashee and his team had to overcome to achieve this feat involved bypassing the bacterial equivalent of an immune system -- essentially a collection of restriction enzymes. These enzymes, thought to have evolved to chew up the genomes of viruses infecting bacterial cells, were preventing the successful transplantation of the modified M. mycoides genome into wild-type M. capricolum. So the group developed two fixes, which together solved the problem: First, they inactivated M. capricolum's restriction enzymes. Then, they chemically modified their mutant M. mycoides genome where these enzymes typically cleave the genomes of intruders.

Decades of research on yeast genetics have yielded the know-how to do extensive genomic manipulations in yeast, but that capability doesn't exist for other microorganisms. "There are so many organisms in nature that we cannot manipulate," said Vashee. "If we can extend this -- and put those genomes into yeast, to manipulate them there -- we've got a new technology that can bring genomics to a wide host of organisms." (Vashee noted that the current study was conducted in a natural Mycoplasma genome -- not the synthetic genome the group assembled last year.)