Researchers at the J. Craig Venter Institute in Rockville, Md., say they've joined together chemically synthesized fragments of DNA to assemble the synthetic genome of the world's smallest free-living bacterium.

Previously, only viral genomes had been synthesized in the lab, but synthesizing the genome of Mycoplasma genitalium, a bacterium that inhabits the genitals and respiratory tracts of primates, represents the first bacterial genome and the largest molecule of defined structure ever made by humans.

The project moved the Venter group a step closer to their ultimate goal of creating the world's first synthetic organism, which then might be used to manufacture biofuels and other compounds.

Harvard geneticist George Church, who was not involved with the study, told The Scientist that it was "an important milestone rather than a breakthrough."

The findings, which appear today (Jan 24) in the online version of Science, follow a paper published by the Venter Institute's synthetic biology and bioenergy group in 2007 showing that it was possible to insert the genome of Mycoplasma mycoides into the closely related Mycoplasma capricolum. (Here is the abstract of the new paper.)

This time, the Venter team pieced together five to seven kilobase-long cassettes of chemically synthesized DNA in vitro to make four 144 kilobase strands of DNA. They then cloned these as bacterial artificial chromosomes in E. coli and transferred the chunks of DNA to yeast cells. There, they were cloned and assembled into a complete 582 kilobase genome, which contains 485 protein-coding genes.

J. Craig Venter, who sits on the scientific advisory board of The Scientist and was an author on the paper, called the study "a very exciting advance" in a press briefing he and his coauthors held today.

Venter said that the next step is to "boot up" the artificial genome by implanting it into a cell and getting that cell to express the synthetic genes. "There are multiple barriers to this," warned Venter. "It isn't just a slam-dunk, or we would be announcing it today."

Other researchers share the Venter group's goal of creating biofuels by co-opting the genetic machinery of microorganisms. Church, who founded the biotech company LS9, said that his company is approaching the challenge from a different angle. At LS9, researchers reprogram the genome of E. coli to metabolically produce a petroleum-like product. Church said he believes LS9's approach may prove to be more efficient.

"It might be that just starting with an organism that has lots of metabolic capabilities already might be a better biological platform," he said. Church suggested that reprogramming an existing genome may turn out to be less costly than completely synthesizing a new genome that requires the use of two other organisms. "LS9 is actually making biofuels with way fewer than 70 changes [to the genome of E. coli]," he said.

Venter explained that another of his companies, Synthetic Genomics, is already altering existing genomes to harvest useful chemicals, but that his current work will usher in a "new design phase of biology."

"Starting with design in the future, I think, will be the method of choice," he said, "once we know in fact it is doable. I am 100 percent certain [this] will be the process of choice."

UPDATE (Jan. 25, 9:37 a.m EST): Link to Science abstract added.