Synthetic yeast as the new frontier in evolutionary developments in biology

When it comes to developments in biology, fueled to a great extent by rapid advances in genomics, the brewing yeast Saccharomyces cerevisiae has served as an important model system (Li and Borodina 2014; Becker and Wittmann 2015; Fletcher, Krivoruchko and Nielsen 2016; Smanski et al.2016). In spite of the increased use of this yeast for a wide range of biotechnological applications, recent developments in the fundamental understanding of this yeast species have been overshadowed by other developments in physics with the hunt for the God particle and by advances in artificial intelligence with increasingly smarter machines that are touted to compete with Homo sapiens for their capability for critical thinking. In the past five years, Saccharomyces cerevisiae, or what should be referred to more appropriately as Syntheomyces cerevisiae, has been undergoing a major evolutionary retooling with the rapid development of synthetic yeast versions by several labs across several continents, with the impetus for the effort by the pioneering work done originally by Jef Boeke and his colleagues at John Hopkins University and more recently at the NYU School of Medicine. The common baking brewer's yeast is now being redesigned and revamped for greater efficiency with the use of editing tools to excise and remove and reconnect DNA sequences to answer the ‘age-old’ question of what constitutes a viable functioning living organism, but without the burden of genetic excess and reduced redundancy. The scientists involved in this endeavor, or what is called the Sc2.0 project, have the goals of preserving in the new strains a high level of fitness comparable to the wild type while at the same time preserving genetic flexibility by removing destabilizing genetic elements such as tRNA or transposons (Dymond et al.2011; Annaluru et al.2014). The new strains will also undergo massive restructuring with de novo synthesis in the laboratory of the 16 chromosomes using a novel method of combinatorial mutagenesis that is capable of generating complex genotypes and a broad range of phenotypes based on a new technique that is referred to as SCRaMbLE (synthetic chromosome rearrangement and modification of the loxP-mediated evolution). The above approaches have opened the door beyond restructuring of the yeast genome to introducing great variations in gene content and copy number as well as to the possibility of genome consolidation and repackaging into fewer chromosomes with changes in ploidy, structure and function. The construction of Sy. cerevisiae with a reduced number of chromosomes from 16 remove down to possibly a single chromosome, while daunting, is increasingly becoming in the realm of the possible with early attempts described in a recent talk by Jef Boeke at the ICY14 conference in Japan. Such development serves as a major step towards evolving greater efficiency of a biological system that in some ways will be as significant as the discovery of the smallest predicted subatomic—or so-called God—particle or the creation of more intelligent interactive machines. The synthetic yeast project is positioning yeast molecular biologists at the crossroads of future advances in science and technology, but many challenges still remain. Can evolution and adaptation be carried out in a streamlined system using synthetic biology tools in a lab on a yeast that Mother Nature has designed for great genetic redundancy and diversity? What constitutes an essential or non-essential gene in Sy. cerevisiae has yet to be defined given the desire at a future date to use these new synthetic yeast strains to produce biomolecules of interest at commercial scale. Past practices in yeast genetic breeding, hybridization and domestication of industrial yeast tell us that such endeavors are challenging, laborious and often unsuccessful (Sanchez, Solodovnikova and Jürgen Wendland 2012; Steensels et al.2014). Saccharomyces cerevisiae by comparison to other yeasts has one of the largest genomes and DNA content, and that may be one of the reasons this yeast has been widely used successfully, with the production of ethanol by fermentation currently being the largest biotechnological application of any microbial system at industrial scale. The staging and scale associated with large-scale production of commodity-type biomolecules requires the preservation of a high degree of genetic redundancy to insure yeast strain robustness under far from ideal industrial production conditions (Wagner 2000; Alam et al.2016). A tour de force approach to evolving new strains will require the introduction of a higher degree of genomic diversity and stability and the importation of new traits from a wider genomic repertoire from other sources such as the so-called non-conventional yeasts. The year 2017, which the various teams have targeted for the completion of their efforts to synthesize all 16 chromosomes and to assemble these into a single strain, should indicate how far this approach—beyond just being exciting science carried out by a highly motivated group of scientists—can be developed to yield beneficial outcomes for society. What is clear from this research is that it will be another milestone on the road of understanding of what is possible to achieve in a relatively short period of time when scientists, using a simple eukaryotic system can, build on knowledge gained from three decades of advances in genomics. With this development, the field of synthetic biology or designer microbes promise to place yeast biologists at the new frontier of science and technology with more exciting developments to come. Conflict of interest. None declared.