Macquarie University researchers and an international team have completed the final chromosome in the world’s first synthetic yeast genome, a significant milestone in synthetic biology.
This accomplishment marks the completion of the global Sc2.0 project, which aimed to create the first synthetic eukaryotic genome using Saccharomyces cerevisiae (baker’s yeast) and a new tRNA no chromosome.
The team used advanced genome-editing techniques, including the CRISPR D-BUGS protocol, to correct genetic errors that affected yeast growth. This enabled the yeast to grow on glycerol at higher temperatures.
This breakthrough demonstrates how engineered chromosomes can be created and improved to make more resilient organisms, potentially securing food and medicine supplies amidst climate change and future pandemics.
Professor Sakkie Pretorius described this achievement as a “landmark moment in synthetic biology,” noting that it completes a puzzle researchers have worked on for years.
Distinguished Professor Ian Paulsen, co-leader of the project, stated that constructing and debugging the final synthetic chromosome has created a powerful platform for engineering biology. This platform could revolutionize the production of medicines, sustainable materials, and other essential resources.
The research team used specialized gene-editing tools to fix issues in the synthetic chromosome that affected yeast reproduction and growth under challenging conditions. They discovered that genetic markers near uncertain gene regions interfered with essential gene functions, impacting crucial processes like copper metabolism and cell division.
Dr. Hugh Goold, a research scientist at The NSW Department of Primary Industries and Macquarie University, emphasized that their key finding was that placing genetic markers in certain positions can disrupt essential gene functions. This discovery is vital for future genome engineering projects and helps establish guidelines for other organisms.
Completing the chromosome known as synXVI opens new possibilities in metabolic engineering and strain optimization. The synthetic chromosome allows scientists to create genetic diversity on demand, speeding up the development of improved yeasts for biotechnology.
Dr. Briardo Llorente, Chief Scientific Officer at the Australian Genome Foundry, highlighted that the synthetic yeast genome represents a significant leap in the ability to engineer biology. Building such a large synthetic chromosome was possible through robotic tools at the Australian Genome Foundry.
Dr. Llorente added that this achievement opens up new possibilities for developing more efficient and sustainable biomanufacturing processes, such as producing pharmaceuticals and creating new materials.
The research offers valuable insights for future synthetic biology projects, including potential applications in engineering plant and mammalian genomes. The team’s new design principles for synthetic chromosomes, which avoid placing disruptive genetic elements near important genes, will aid other researchers.
Macquarie University contributed over 12 percent to the entire 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 grants from Bioplatforms Australia and the NSW Chief Scientist and Engineer.
Journal Reference:
- Goold, H.D., Kroukamp, H., Erpf, P.E. et al. Construction and iterative redesign of synXVI, a 903 kb synthetic Saccharomyces cerevisiae chromosome. Nat Commun 16, 841 (2025). DOI: 10.1038/s41467-024-55318-3
Source: Tech Explorist
