Engineering a modular and minimal synthetic genome

We aim to build a modular and minimal synthetic yeast genome (Sc3.0) through extensive genome engineering and refactoring. Recent breakthroughs in DNA synthesis and editing techniques have ushered in a new era of genome engineering, allowing researchers to comprehensively manipulate an organism's entire genetic blueprint. This advancement provides an invaluable toolbox for directly investigating the intricate links between an organism's genotype and its observable traits, or phenotype. Genome synthesis not only grants researchers unprecedented control over organisms but also opens up a novel avenue for deepening our understanding of genome biology.
Through careful design, the synthetic yeast genome (Sc2.0, www.syntheticyeast.org) project has enabled experimental tests of many otherwise intractable questions about chromosome function and evolution. For example, removal of all retrotransposons and LTR repeats has produced a genome free of mobile elements, providing a system to assay effects of mobile elements on genome stability directly. Nevertheless, Sc2.0 made minimal changes to non-coding regions, no changes in gene order, and deletions of very limited number of genes. Complementary to Sc2.0, the Sc3.0 genome would allow to further explore questions such as how much of the yeast genome is redundant and could be compacted? What is the content of a minimal genome to support life under a given condition? Is the gene organization in the current genome evolutionary inevitable or contingent?
As a first step, all essential genes from each chromosome will be restructured with designated regulatory elements. Next, each could be functionally validated and assembled into a dedicated chromosome with altered gene orders. Finally, the newly synthesized Sc3.0 chromosomes could then be combined into a single yeast to obtain strains with multiple chromosomes, or alternatively, these chromosomes could be merged into a single large chromosome. Once this essential synthetic chromosome is completed, we will deploy the SCRaMbLE (synthetic chromosome rearrangement and modification by loxP-mediated evolution) to minimize the genome.