Synthetic Biology Avoiding the Chop

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Nature Reviews Genetics | AOP, published online 15 september 2009; doi:10.1038/nrg2671

SyNtHEtIC bIOLOGy Avoiding the chop

Over the past few years researchers First, they transformed bacteria methylation using M. capricolum have made substantial progress in the (Mycoplasma mycoides) with a vector or M. mycoides cellular extracts or quest to create synthetic microorgan- containing sequences that would purified methylases. Both of these isms, for which a necessary step is the allow the M. mycoides genome to strategies worked, and implementa- transplantation of a synthetic genome propagate in yeast as an artificial tion of either allowed M. mycoides into a bacterial cell. However, until chromosome. They then transferred genomes that had been modified in now, this has proved to be an elusive this M. mycoides genome to yeast yeast to be successfully transplanted goal. Therefore, the recent transplan- and found that it could be stably into M. capricolum cells. tation and modification of a bacterial maintained. By inserting a cas- As there are few selection mark- genome in yeast and the transfer of sette with yeast selection markers ers that can be used in mycoplasma this genome to a different bacterial into the bacterial genome, they systems and these bacteria have low strain to produce viable cells is an deleted a non-essential restriction recombination activity, the genetic important advance for the synthetic endonuclease from the M. mycoides manipulation of M. mycoides is biology field. genome — demonstrating that yeast limited. However, the maintenance of J. Craig Venter and colleagues tools can be used to modify bacterial bacterial genomes in yeast described …the previously demonstrated that the genomes outside their native cellular in this study will allow the manipula- maintenance genome of one bacterium could be environment. tion of bacterial genomes through of bacterial replaced with that of another and However, when the authors the vast array of genetic tools that genomes in reasoned that the same would be true tried to transplant M. mycoides can be implemented in yeast. This for a synthetic genome. However, genomes from yeast to recipient opens up the possibilities of creating yeast described when they chemically synthesized Mycoplasma capricolum cells, once complex genome modifications, such in this study a bacterial genome, assembled it in a again they failed to recover any as multiple deletions, insertions and will allow the yeast system and tried to transplant transplanted cells. They guessed rearrangements, and producing novel the synthetic genome into a different that the unmethylated transplanted bacterial genomes with altered traits. manipulation recipient strain, they were unable to M. mycoides genomes were being The next challenge will be to apply of bacterial recover any transformed cells. digested by restriction enzymes in this strategy to bacterial species other genomes… The authors took a new route to the recipient strain — an important than mycoplasmas, as many micro- work out what the roadblock was. bacterial defence against foreign organisms of clinical or industrial DNA. To overcome this defence, importance are difficult to genetically the authors tried two strategies: manipulate. first, they knocked out the only Meera Swami restriction enzyme in M. capricolum cells; and second, they protected the ORIGINAL RESEARCH PAPER Lartigue, C. et al. Creating bacterial strains from genomes that have donor M. mycoides DNA by in vitro been cloned and engineered in yeast. Science ComStock 20 Aug 2009 (doi:10.1126/science.1173759) fuRtHER REAdING Benner, S. A. & Sismour, A. M. Synthetic biology. Nature Rev. Genet. 6, 533–543 (2005)