Synthetic genomics: from genetic parts to genomes

The Synthetic Yeast genome project, or Sc2.0 (www.syntheticyeast.org <http://www.syntheticyeast.org>), aims to design, construct, and replace the native 12Mb genome of Saccharomyces cerevisiae with a fully synthetic version. Sc2.0 chromosomes encode a myriad of designer changes. First, to improve genomic stability, destabilizing elements such as transposons and tRNA genes are removed from the synthetic genome. Second, synonymously recoded sequences called PCRtags permit encryption and tracking of the synthetic DNA. Finally, to enable downstream genetic flexibility, Sc2.0 encodes an inducible evolution system called SCRaMbLE (Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution) that can generate combinatorial genetic diversity on command. To date, ~70% of the genome has been synthesized and we have powered a semi-synthetic yeast entirely dependent on multiple synthetic chromosome arms designed to our specifications. Software and experimental infrastructure developed to facilitate Sc2.0 genome design and construction are applicable to new projects ranging from single gene/pathway design to synthesizing artificial chromosomes.