Science: Researchers Are the First to “Boot Up” a Bacterial Cell with a Synthetic Genome

Schematic of the assembly of a synthetic M. mycoides genome in yeast. In the first step (orange arrows), short sets of synthetic DNA base pairs are recombined into larger (blue arrows) and larger (green arrows) DNA assemblies. In the final stage of assembly, eleven large DNA fragments are recombined into the complete genome (red circle).

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Image courtesy of Science/AAAS

Scientists have developed the first cell controlled by a synthetic genome, and now hope to use this method to probe the basic machinery of life and to engineer bacteria specially designed to solve environmental or energy problems.

The study was published online by the journal Science, at the Science Express website, on Thursday, 20 May. The Science authors discussed their findings in a Thursday press conference at the Newseum in Washington, D.C.

The research team, led by genetic research pioneer J. Craig Venter, has already chemically synthesized a bacterial genome, and it has transplanted the genome of one bacterium to another. Now, the scientists have put both methods together, to create what they call a “synthetic cell,” although only its genome is synthetic.

“This is the first synthetic cell that’s been made, and we call it synthetic because the cell is totally derived from a synthetic chromosome, made with four bottles of chemicals on a chemical synthesizer, starting with information in a computer,” said Venter, the founder, president, and chairman of the J. Craig Venter Institute.

“This becomes a very powerful tool for trying to design what we want biology to do. We have a wide range of applications [in mind],” he said.

For example, the researchers are planning to design algae that can capture carbon dioxide and make new hydrocarbons that could go into refineries. They are also working on ways to speed up vaccine production. Making new chemicals or food ingredients and cleaning up water are other possible benefits, according to Venter.

In the Science study, the researchers synthesized the genome of the bacterium M. mycoides and added DNA sequences that “watermark” the genome to distinguish it from a natural one.

Because current machines can only assemble relatively short strings of DNA letters at a time, the researchers inserted the shorter sequences into yeast, whose DNA-repair enzymes linked the strings together. They then transferred the medium-sized strings into E. coli bacteria and back into yeast. After three rounds of assembly, the researchers had produced a genome over a million base pairs long.

The scientists then transplanted the synthetic M. mycoides genome into another type of bacteria, Mycoplasm capricolum. The new genome “booted up” the recipient cells. Although 14 genes were deleted or disrupted in the transplant bacteria, they still looked like normal M. mycoides bacteria and produced only M. mycoides proteins, the authors report.

“This is an important step we think, both scientifically and philosophically. It’s certainly changed my views of the definitions of life and how life works,” Venter said.

Acknowledging the ethical discussion about synthetic biology research, Venter explained that his team asked for a bioethical review in the late 1990s and has participated in variety of discussions on the topic.

“I think this is the first incidence in science where the extensive bioethical review took place before the experiments were done. It’s part of an ongoing process that we’ve been driving, trying to make sure that the science proceeds in an ethical fashion, that we’re being thoughtful about what we do and looking forward to the implications to the future,” he said.

This research was funded by Synthetic Genomics, Inc. Three of the authors and the J. Craig Venter Institute hold Synthetic Genomics, Inc. stock. The J. Craig Venter Institute has filed patent applications on some of the techniques described in this paper.

Kathy Wren

20 May 2010