The dawn of synthetic genomics

The first month of 2008 was unusually quiet in terms of microbial genome sequencing. Still, even the relatively short list of newly released genomes includes several interesting environmental microorganisms, such as the anoxygenic phototroph Chloroflexus aurantiacus, the toxic bloom-forming cyanobacterium Microcystis aeruginosa, and the methylotroph Methylobacterium extorquens (Table 1). However, arguably the biggest news was the announcement by J. Craig Venter and colleagues that they ‘have synthesized a 582 970 bp Mycoplasma genitalium genome’ (Gibson et al., 2008). The authors used chemically synthesized oligonucleotides ∼50 nucleotides in length to assemble ‘cassettes’ 5–7 kb in length, then to join them by in vitro recombination to produce intermediate assemblies, gradually increasing in size. Finally, four 144 kb pieces were cloned in Escherichia coli as bacterial artificial chromosomes, transferred into yeast and assembled into a full-length genome. The genome of the resulting strain, named M. genitalium JCVI-1.0, was virtually identical to the genome of the original strain M. genitalium G37. It was not immediately clear whether this technically very challenging and truly monumental work had any purpose beyond just serving as a proof of principle. However, J. C. Venter and colleagues have a record of overcoming enormous technical challenges and launching entirely new areas of biotechnology. It might be simply too early right now to ask them to explain the future of this work. In any case, the era of synthetic biology has officially begun and who knows what kind of molecules people will be synthesizing 10 or 20 years from now.