Synthetic yeast from 2.0 to 3.0

Views:2793       Publish Time: 2017-11-09

The Synthetic Yeast Genome Project (Sc2.0) is the world’s first synthetic eukaryotic genome project that aims to create a novel, rationalized version of the genome of the yeast species Saccharomyces cerevisiae. 

The famous quote from the physicist Richard Feynman "What I cannot create, I do not understand" demonstrates well that the ultimate understanding of the nature will lead to the ability of creating new matters, and in turn the creation will contribute to a better understanding. Biology is now undergoing a transition from the age of deciphering DNA sequence information of the genome of biological species to an age of building synthetic genomes to better understand the principles of life. This transition has been formalized as a new discipline referred to as "Synthetic Biology" (SynBio). Despite its early stage, SynBio has already shown great potential to make significant scientific breakthrough, which will improve the living conditions of human beings. For example, engineering metabolic pathways of yeast to produce the antimalarial drug precursor artemisinic acid; using engineered microorganisms to convert biomass to biofuel as a replacement of fossil fuel; and utilizing engineered bacteriophage as adjuvants for antibiotic therapy. 

The ability to design and synthesize synthetic genomes opens up the possibility to develop microbial solutions to societal problems such as energy crisis. In collaboration with several labs around the world, we are contributing to the largest synthetic biology project ever - the Sc2.0 project. We redesigned the chromosome XII aimed at a) maintaining a wild-type phenotype, b) producing a more stable genome by removing the destabilizing elements such as transposons, c) embedding elements designed to maximize future genetic flexibility such as recoding the stop code TAG to TAA and the incorporation of symmetrical loxP sites throughout the chromosome. In 2017, the global Sc2.0 team has built five new synthetic yeast chromosomes, meaning that 30 percent of S.cerevisiae’s genetic material has now been swapped out for engineered replacements. On March 10th, a package of seven papers published March 10 as the cover story for Science.

We have a better understanding of how yeast genome works after synthesizing yeast genome. Based on what we learned from Sc2.0, we are aiming to re-design a yeast genome with well-known regulatory elements and codon optimized open reading frames. By doing this, we could engineer a simpler yeast genome, which gives us an opportunity to explore the folding and stabilizing mechanisms of eukaryotic chromatin.