Synthetic Biology Creates Designer Microbes for Environmental Applications

Each living organism has a genetic code that determines its characteristics and properties. The genetic material carries the history of the organism’s development through generations – mutations, selection, and combinations. Each organism is a product of its parents, a combination of their genetic codes (or the clone of its parent cell’s genome for asexually reproducing organisms). In May 2010, synthetic biology took its first large step towards it aim of developing microbes for medical and environmental applications; researchers at the J. Craig Venter Institute in Maryland announced that they had created the first cell with a synthetic genome – a genome designed by a computer and with no specific parental or generational history. Their work was published in the journal Science (a summary is available from TheScientist).

However, it is not a new organism. The researchers used the known sequence of the bacteria Mycoplasma mycoides. This bacteria grows relatively quickly and has a genome 1 million bases in length. The researchers ordered pieces of the genome from a DNA sequence manufacturer, which specialize in combining nucleotides to make sequences several hundred base pairs in length. These synthetic DNA sequences are used in a number of research applications. Yeast were then used to combine the sequences into longer genetic sequences, finally achieving the whole genome.

The stitched together genome was transferred into a surrogate cell of the bacterium Mycoplasma capricolum to create the cell with the first synthetic genome. The cell exhibited the characteristics and properties of a M. mycoides cell and was capable of replication. This is a proof of concept for the technique, but it didn’t happen on the first try. The team of 20 scientists spent a decade, with a failed transfer attempt of a natural chromosome in 2007, to get to this point.

Methylation was found to be an issue with transferring natural genomes, but this problem is not present with the synthetic genomes, allowing the recipient to accept it. Their first attempt with transferring the synthetic genome also did not work – because of a single mistaken base. Replacing the errant piece of DNA gave them the results they were looking for on the next try. The synthetic genome also contains four coded messages – a message from the creators so to speak.

The first application is expected to debut as early as next year from among two current projects. ExxonMobil and the J. Craig Venter Institute are working on synthetic algae that capture carbon dioxide and produce fuel, and the institute and the National Institutes of Health, along with Novartis, are attempting to apply the knowledge to vaccine production. More information on applications in fuel production can be found at SyntheticGenomics.

The researchers expect future obstacles to include how to design and synthesize novel synthetic sequences of choice that will result in a living cell.

The paper is available as: D.G. Gibson et al. “Creation of a bacterial cell controlled by a chemically synthesized genome,” Science, published online May 20, 2010, doi: 10.1126/science.1190719. Craig Venter also gave a TedTalk on the advance that is available on YouTube.