Scientists have successfully finished constructing the last chromosome of the first synthetic yeast genome, marking a significant advance after over ten years of dedicated research. This breakthrough offers exciting opportunities to design resilient, engineered organisms.
Researchers from Macquarie University, in collaboration with an international team, have reached a key milestone in synthetic biology by finalizing the first synthetic yeast genome’s last chromosome.
This accomplishment signifies the conclusion of the global Sc2.0 project, which aimed to develop the world’s first synthetic eukaryotic genome from Saccharomyces cerevisiae (commonly known as baker’s yeast) and an entirely new tRNA neochromosome.
Employing advanced genome-editing methods, such as the CRISPR D-BUGS protocol, the researchers were able to identify and rectify genetic flaws that had been hindering yeast growth. These modifications restored the strain’s capability to grow on glycerol, a critical carbon source, even at higher temperatures.
This significant finding, reported this week in Nature Communications, illustrates how synthetic chromosomes can be constructed, developed, and refined to engineer more robust organisms, which could play a crucial role in maintaining food and medicine production amidst challenges posed by climate change and potential pandemics.
“This represents a historic achievement in synthetic biology,” states Professor Sakkie Pretorius, Co-Chief Investigator and Deputy Vice Chancellor (Research) at Macquarie University.
“It completes a long-standing puzzle that has preoccupied synthetic biology researchers for years.”
Distinguished Professor Ian Paulsen, who co-led the project and is the Director of the ARC Centre of Excellence in Synthetic Biology, adds: “Our success in constructing and refining the final synthetic chromosome provides a potent foundation for biological engineering that could transform the production of medicines, sustainable materials, and other essential resources.”
The research team employed advanced gene-editing tools to pinpoint and rectify issues in the synthetic chromosome that affected the yeast’s ability to reproduce and thrive under tough conditions.
They found that the placement of genetic markers close to uncertain gene regions inadvertently hindered the regulation of vital genes, particularly impacting key functions such as copper metabolism and how cells manage their genetic material during division.
“A significant finding was how the positioning of genetic markers could disrupt the activation of essential genes,” explains co-lead author Dr. Hugh Goold, a research scientist at The NSW Department of Primary Industries and an Honorary Postdoctoral Research Fellow at Macquarie University’s School of Natural Sciences.
“This insight carries significant implications for future genome engineering efforts, establishing design principles applicable to various organisms.”
The conclusion of synXVI, the synthetic chromosome, enables researchers to investigate innovative approaches in metabolic engineering and enhancing yeast strains. This synthetic chromosome contains features that allow scientists to generate genetic diversity on demand, speeding up the development of yeasts suitable for biotechnological applications.
“The synthetic yeast genome marks a major advancement in our capability to engineer biological systems,” asserts Dr. Briardo Llorente, Chief Scientific Officer at the Australian Genome Foundry.
The creation of such a complex synthetic chromosome was made feasible through the use of robotic technologies at the Australian Genome Foundry.
“This achievement introduces thrilling possibilities for crafting more efficient and sustainable biomanufacturing methods, applicable in producing drugs and developing new materials,” notes Dr. Llorente.
The research offers valuable insights for upcoming synthetic biology initiatives, including opportunities to engineer genomes in plants and mammals. The team’s novel design principles for synthetic chromosomes aim to prevent placing potentially disruptive genetic elements near significant genes, aiding other researchers in their synthetic chromosome projects.
Macquarie University accounts for over 12 percent of the total contribution to the Sc2.0 project, supported by the NSW Government’s Department of Primary Industries, the Australian Research Council Centre of Excellence in Synthetic Biology, and external funding from Bioplatforms Australia and the NSW Chief Scientist and Engineer.
