1st cell with synthetic genome

After a 15-year marathon, researchers have created the first cell controlled by a synthetic genome, reported online today at Science.

The advance, a landmark in synthetic biology, could someday be used to engineer microbes for environmental or medical applications.

“This is a very impressive piece,” said Jim Collins, a bioengineer at Boston University, who was not involved in the study. The research is a “methodological tour de force,” said Collins.

Images of synthetic (top, expressing
blue reporter genes) and wildtype
(bottom) M. mycoides strains

Image courtesy of Science/AAAS

Combining a series of techniques developed since 1995, J. Craig Venter and colleagues at the J. Craig Venter Institute in Rockville, Maryland began with a digitized genome sequence of Mycoplasma mycoides, a fast-growing bacterium with a 1-million-base genome. They ordered the pieces of that genome from a DNA sequence manufacturer, then used yeast to stitch the pieces together into a whole genome. The researchers transferred the synthetic M. mycoides genome into a M. capricolum recipient cell, replacing the native DNA, and the cell successfully booted up the new genome. The finished product was capable of replication and had all the expected properties of a M. mycoides cell.

“They are living cells,” Venter told The Scientist. “The only difference is they have no natural history. Their parents were the computer.”

The effort cost an estimated $40 million, with 20 people working for more than a decade, according to Science. “It was one hurdle after another,” said Venter (who is a member of The Scientist’s editorial board). In 2007, when the team first tried to transplant a natural chromosome from one bacterial species to another, it didn’t work. They soon realized the problem was methylation: The transplanted DNA didn’t have the same methylation patterns as the excised DNA, so the recipient cell’s restriction system chewed up the foreign DNA. “It took two years to solve that problem,” said Venter.
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