Whole Genome Engineering in Saccharomyces cerevisiae –An introduction to synthetic biology and the Yeast 2.0 project
The prevailing ethos in the emerging field of synthetic biology is to understand biology through engineering and re-design. This approach has been directed towards the construction of novel genetic regulatory circuits, altered metabolic pathways, and even whole genomes. The ‘Yeast 2.0’ project is an international synthetic biology collaboration aimed at building a fully synthetic Saccharomyces cerevisiae genome by 2017. Although only modest changes are being made to the natural genome sequence, an inducible evolution system in being incorporated into the synthetic genome that can result in large-scale genomic rearrangements. This ‘Synthetic Chromosome recombination and Modification by LoxP Mediated Evolution’ (SCRaMbLE) system will be used to generate millions of unique genomes with varied architecture and gene content. By placing appropriate selection pressure on SCRaMbLEd populations, cells with minimal genomes or superior industrial properties can be recovered. Sequencing the genomes of these isolates will then be carried out with the goal of revealing novel ‘design principles’ for rational engineering, fulfilling the synthetic biology mandate to learn by building.