Molecular Systems Biology | The Seven Stones

[Research highlight] Mycoplasma rebooted

Upshot of a series of four papers published over the last years (Gibson et al, 2010, Lartigue et al, 2009, Gibson et al, 2008, Lartigue et al, 2007), J. Craig Venter’s team now reports the successful transplantation of a chemically synthesized genome into a host bacterial cell (Gibson et al, 2010). As proof of principle, a slightly altered Mycoplasma mycoides genome (JCVI-syn1.0) was synthesized, assembled and transplanted into M. capricolum recipient cells.

This achievement results from the integration of several techniques developed in previous works: 1) a hierarchical strategy to assemble, via homologous recombination in yeast, a full genome from chemically synthesized overlapping fragments (Gibson et al, 2008); 2) a method to transform a full genome into a host cell and replace the recipient genome by the donor genome (‘transplantation’, Lartigue et al 2007); 3) a method to transplant DNA engineered in yeast into bacteria without being inactivated by the host restriction system (Lartigue et al, 2009). Finally, in the last work, systematic debugging methods were needed to identify a single base pair deletion that prevented productive transplantation (Gibson et al 2010).

The experiment represents certainly a highly symbolic milestone. A fascinating potential of this technology, if generalized and automated, is to enable the introduction of many genomic alterations simultaneously and, thus, to be able to reprogram cellular phenotypes with non-trivial genetic combinations that would have been impossible to identify with a sequential gene by gene approach. In this sense, while technically and ‘philosophically’ distinct, Venter’s approach appears complementary to multiplexed mutagenesis technologies that introduce simultaneously multiple modifications in a target genome (Wang et al, 2009).

Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GW, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi, ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA, Smith HO, Venter JC (2010). Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome. Science advance online publication doi: 10.1126/science.1190719

Lartigue C, Vashee S, Algire MA, Chuang RY, Benders GA, Ma L, Noskov VN, Denisova EA, Gibson DG, Assad-Garcia N, Alperovich N, Thomas DW, Merryman C, Hutchison CA 3rd, Smith HO, Venter JC, Glass JI (2009). Creating bacterial strains from genomes that have been cloned and engineered in yeast. Science 325:1693

Gibson DG, Benders GA, Andrews-Pfannkoch C, Denisova EA, Baden-Tillson H, Zaveri J, Stockwell TB, Brownley A, Thomas DW, Algire MA, Merryman C, Young L, Noskov VN, Glass JI, Venter JC, Hutchison CA 3rd, Smith HO (2008). Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome. Science 319:1215

Lartigue C, Glass JI, Alperovich N, Pieper R, Parmar PP, Hutchison CA 3rd, Smith HO, Venter JC (2007). Genome transplantation in bacteria: changing one species to another. Science 317:632

Wang HH, Isaacs FJ, Carr PA, Sun ZZ, Xu G, Forest CR, Church GM (2009). Programming cells by multiplex genome engineering and accelerated evolution. Nature 460:894


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