The Next Steps in Synthetic Biology

The advent of genome sequencing and analysis, coupled with the relative simplicity of DNA synthesis, has given rise to the field of synthetic biology. Described in 1974 by Waclaw Szybalski, the practice of synthetic biology would include the ability to "devise new control elements and add these new modules to the existing genomes or build up wholly new genomes."

More than 20 years later, this description is being realized. With the great minds and funds of the Venter Institute, we have seen the development of a completely synthetic genome and whole genome transplantation. The genome of Mycoplasma genitalium (at ~580Kbp) was synthesized primarily in vitro before being pieced together in Saccharomyces cereviseae. The whole genome of M. mycoides was transplanted into M. genitalium, changing the metabolism, physiology, structure, and subsequently the species of the recipient.

Now, this group has taken this technology one step further. The synthetic genome they pieced together in yeast, must be isolated and transplanted into a donor cell; thus completing the construction of a synthetic, replicating organism.

In a soon-to-be published article in Science, the group describes a method for modifying the complete bacterial genome while in yeast, and then transferring the modified genome back into the original cell. This process allows bacterial genomes to be modified using the well-described genetic systems in yeast, before being introduced. Thus, new possibilities are open for bacteria that once had little to no genetic tools available.

The authors emphasize this development as it directly relates to Mycoplasma biology. They focus on the fact that Mycoplasma and related species now have an entire repertoire of manipulations available to them, however, the ramifications of this experiment certainly do not escape them and should not escape us.

This is the first example of a bacterial cell being created and engineered completely outside the cell itself. Although the recipient cell began with all the necessary physical components for life, this group synthetically created a new organism to control and change those components. This is the closest we have come to synthesizing an organism from scratch.

Some may say this is playing God; however, it will certainly have a positive impact on the development of biofuels, environmental remediation, and chemical synthesis on an industrial scale.

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Citation:
Lartigue, C., Vashee, S., Algire, M., Chuang, R., Benders, G., Ma, L., Noskov, V., Denisova, E., Gibson, D., Assad-Garcia, N., Alperovich, N., Thomas, D., Merryman, C., Hutchison, C., Smith, H., Venter, J., & Glass, J. (2009). Creating Bacterial Strains from Genomes That Have Been Cloned and Engineered in Yeast Science DOI: 10.1126/science.1173759

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