Construction of a synthetic Saccharomyces cerevisiae pan-genome neo-chromosome

The Synthetic Yeast Genome Project (Sc2.0) represents the first foray into eukaryotic genome engineering and a novel framework for designing and building the next generation of industrial microbes. However, the laboratory strain S288c used lacks many of the genes that provide phenotypic diversity to industrial and environmental isolates. To address this shortcoming, a completely novel, neo-chromosome that contains many of these diverse pan-genomic elements and which is compatible with the Sc2.0 design and test framework has been engineered and constructed. The presence of this neo-chromosome was shown to provide phenotypic plasticity to the Sc2.0 parent strain, including expanding the range of utilizable carbon sources. The induction of programmable structural variation (SCRaMbLE) was also demonstrated as a means of providing genetic diversity on which further adaptive gains could be selected. The presence of this neo-chromosome within the Sc2.0 backbone could therefore provide the means to adapt synthetic strains to a wider variety of environments, a process which will be vital to transitioning Sc2.0 from the laboratory into industrial applications.

合成酵母基因组计划（Sc2.0）是真核基因组工程领域的开创性探索，同时也是设计构建下一代工业微生物的全新框架。然而其所使用的实验室菌株S288c，缺失了诸多赋予工业与环境来源分离株表型多样性的基因。为弥补这一短板，研究人员设计并构建了一条全新的新染色体（neo-chromosome），其携带有诸多上述多样化的泛基因组元件，且可兼容Sc2.0的设计与测试框架。实验证实，该新染色体的引入可赋予Sc2.0亲本菌株表型可塑性，包括拓展其可利用碳源的范围。此外，可编程结构变异诱导系统（SCRaMbLE）的诱导应用也得到验证，该系统可作为生成遗传多样性的手段，进而筛选获得适应性更强的菌株。因此，在Sc2.0基因组骨架中引入该新染色体，可使合成菌株适应更多样化的环境，这一过程对于推动Sc2.0从实验室研究迈向工业应用至关重要。