Published online 20 August 2009 | Nature | doi:10.1038/news.2009.847

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Scientists devise new way to modify organisms

Yeast cell surrogate may help scientists to engineer synthetic life.

Mycoplasma mycoidesA modified genome from one bacteria has been inserted into another.J. Craig Venter Institute.

Scientists have devised a way to modify an organism that was previously impossible to genetically engineer in the lab.

The method, developed by researchers at the J. Craig Venter Institute in Rockville, Maryland, and San Diego, California, could aid the development of biomaterials and biofuels by helping scientists to genetically engineer species that have so far been beyond their reach. It could also aid the Venter institute's project to create synthetic life.

In their paper, published today in Science1, the researchers describe how they removed a genome from the bacterium Mycoplasma mycoides and transplanted it into the yeast Saccharomyces cerevisiae. They were then able to delete a gene from the M. mycoides genome — a feat that would not have been possible in the bacterium, because scientists lack the tools to genetically engineer the organism.

The team then inactivated an enzyme in a related bacterium, called Mycoplasma capricolum, that defends against invading organisms by destroying DNA that has not been tagged with certain chemical modifications, called methyl groups. The team also artificially added methyl tags to the M. mycoides genome to enable the bacterium to get past M. capricolum 's defences.

The bioengineers then transplanted the modified M. mycoides genome into M. capricolum, where it was able to direct the M. capricolum cells to form colonies of M. mycoides.

"There are many synthetic-biology applications that need modification of bacteria on a large scale, and yet many organisms that are of interest in this space are not easy to manipulate genetically," says James Collins, a bioengineer at Boston University in Massachusetts, who was not involved with the research. "So this is really quite a nice advance from a genome engineering standpoint."

Last year, the Venter institute reported that it had synthesized the genome of a small bacterium, Mycoplasma genitalium, by stitching together fragments of it in yeast cells2. The institute has also transplanted the unmodified genome of M. mycoides into an M. capricolum bacterium3.

Tricky transplant

What researchers have not yet been able to do is transplant either a synthetic or native M. genitalium genome into Mycoplasma pneumoniae and 'boot up' the recipient bacteria with the new genetic code. That project has been hampered in part by the fact that M. genitalium grows very slowly, so it is difficult to explore the conditions that would allow a successful genome transplantation, the authors of the paper say. But the ability to manipulate the M. genitalium bacterium in yeast cells might also allow the team to remove any barriers that may stand in the way of a transplantation, the researchers say.

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Overcoming these barriers are essential if bioengineers are to create synthetic life, says study author John Glass from the institute in Rockville. But Glass says that it is difficult to predict when that might happen. "It could be tomorrow, or it could be next year," he says. "We have yet to transplant a native M. genitalium into M. pneumoniae, and we're feverishly working on it, but we haven't got there yet."

Collins is confident that groups will soon be able to take that step, and that they will bill it as the first synthetic organism. "We'll probably see something like that in the next few months and groups will be pitching it as the first synthetic organism," he says. But Collins has stricter criteria for what constiutes synthetic life. "My sense of a synthetic organism is one you build from scratch — in that you're not basing the genome directly on an extant natural genome — and we're very far away from doing that," he says. 

  • References

    1. Lartigue, C. et. al. Science advance online publication doi:10.1126/science.1173759 (2009).
    2. Gibson, D. G. et al. Science 319, 1215-1220 (2008). | Article | PubMed | ChemPort |
    3. Lartigue, C. et al. Science 317, 632-638 (2007). | Article | PubMed | ChemPort |
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