Craig Venter's Team Reports Key Advance in Synthetic Biology

Researchers at the J. Craig Venter Institute (JCVI), a genomic research organization, reported that they successfully transformed one bacterium into a different strain by transferring the entire bacterial genome of the first strain into a second, related strain of bacteria. In order to accomplish this feat, the team performed what they called a genetic first: they transferred genes from a prokaryote to a eukaryote and back to a prokaryote. The genetic manipulations they performed represent an important advance in synthetic biology.

The researchers published results (1) last week describing how they removed a genome from the bacterium Mycoplasma mycoides, re-engineered and reproduced it inside the yeast Saccharomyces cerevisiae (a eukaryote), and then transplanted the engineered genome into Mycoplasma capricolum, thus effectively turning it into a new strain of M. mycoides. The researchers had to develop new methods in which the entire bacterial genome from Mycoplasma mycoides was cloned in the yeast cell, according to a JCVI press release. The techniques used in this work pave the way for future groups to create novel genomes, which may allow them to create novel cells with novel properties.

“I believe this work has important implications in better understanding the fundamentals of biology to enable the final stages of our work in creating and booting up a synthetic genome,” said Hamilton Smith, a JCVI scientist and Nobel Laureate, in the release. “This is possibly one of the most important new findings in the field of synthetic genomics.”

In this study, the team cloned the native M. mycoides genome into yeast by adding a yeast centromere to the bacterial genome, which the researchers say is the first time a native bacterial genome has been grown successfully in yeast. Further manipulations were required to prevent the recipient bacterium from disabling the transplanted genome. For example, the engineered genome could be successfully transplanted into wild-type M. mycoides if it were first methylated. In other experiments, the engineered genome could be successfully transferred following the removal of the genes encoding restriction enzymes from recipient bacterium’s DNA.

“The ability to modify bacterial genomes in yeast is an important advance that extends yeast genetic tools to bacteria,” said Sanjay Vashee, JCVI researcher, in the release. “If this is extendable to other bacteria, we believe that these methods may be used in general laboratory practice to modify organisms.”

With its efforts, the researchers have a complete cycle of cloning a bacterial genome in yeast, modifying the bacterial genome to make it behave as though it were a yeast chromosome, and transplanting the genome back into a recipient bacterial cell to create a new bacterial strain. These new methods and knowledge should allow the team to now transplant and boot up the synthetic bacterial genome successfully, according to the release.

The research by JCVI was funded by Synthetic Genomics (SGI, LaJolla, CA), a company focused on commercializing genomic-driven technologies and cofounded by Smith and Venter. SGI believes that a synthetic chromosome, and eventually synthetic cells, will become integral tools for industrial applications, including the development of biofuels and chemicals based on renewable resources, according to company information. In July, the company formed an alliance with Exxon Mobil (Iriving, TX) to research and develop next-generation biofuels from photosynthetic algae.

Synthetic biology shows strong market potential
The field of synthetic biology is still emerging, but market analysts are optimistic about its commercial potential. The global market for synthetic biology was $233.8 million in 2008, according to a June 2009 report by Business Communications Company (BCC), a Norwalk, Connecticut-based market research firm. This value is expected to increase to $2.4 billion in 2013, for a compound annual growth rate (CAGR) of 59.8%.

Chemicals and energy represent the largest market segment for synthetic biology, which was valued at $80.6 million in 2008, and is projected to reach $1.6 billion in 2013, for a CAGR of 81.6%, according to BCC. The biotechnology and pharmaceuticals segment is the second-largest market sector, valued at approximately $80.3 million in 2008. This segment is projected to increase at a CAGR of 49.2% to reach $594 million in 2013, according to BCC.

Reference
1. C. Lartigue et al., “Creating Bacterial Strains from Genomes That Have Been Cloned and Engineered in Yeast,” Science, online Aug. 20, 2009, DOI 10.1126/science.1173759.