Researchers Complete World’s First Synthetic Yeast Genome, Pioneering Advances in Biomanufacturing and Synthetic Biology

January 27, 2025

Researchers from Macquarie University, alongside an international team, have achieved a groundbreaking milestone in synthetic biology. The final phase of synthetic chromosome research was completed in Saccharomyces cerevisiae genome. This landmark was part of the Sc2.0 mission to create a completely synthesised eukaryotic genomic structure.

Scientists developed this synthetic yeast genome with a novel tRNA neochromosome. The discovery enables research into genetically engineered organisms that push the boundary of the development of pharmaceuticals and sustainable materials in biomanufacturing.

The research team applied CRISPR D-BUGS protocol, a cutting edge genome editign technique, in combination with other genome-editing methods to fix genetic issues that controlled yeast growth patterns. Authorship of CRISPR D BUGS protocols allowed researchers to recover glycerol carbon utilisation at elevated temperatures for their strain.

“This is a landmark moment in synthetic biology,”

Stated Professor Sakkie Pretorius, Deputy Vice Chancellor (Research) at Macquarie University. He went onto say:

“It is the final piece of a puzzle that has occupied synthetic biology researchers for many years now.”

Professor Ian Paulsen, Director of the ARC Centre of Excellence in Synthetic Biology, who co-led the project, stated:

“By successfully constructing and debugging the final synthetic chromosome, we’ve helped complete a powerful platform for engineering biology that could revolutionise how we produce medicines, sustainable materials and other vital resources.”

The research implementation encountered several difficulties along the way. The researchers experienced limitations in yeast growth because the genetic markers blocked crucial gene functioning. The project benefited from utilising CRISPR D-BUGS and other genome-editing instruments which both identified and corrected defects within the synthetic chromosome structure for yeast survival during difficult conditions.

“These insights have far-reaching implications for future genome engineering,”

noted Dr. Hugh Goold, co-lead author and research scientist at The NSW Department of Primary Industries.

The final chromosome, synXVI, is equipped with features that allow for the generation of genetic diversity on demand. This capability accelerates the optimisation of yeast strains for various applications, such as biofuel production, medicine manufacturing, and sustainable material synthesis.

The scale and complexity of constructing synXVI were made possible by robotic instrumentation at the Australian Genome Foundry. Dr. Briardo Llorente, Chief Scientific Officer at the Foundry, emphasizes that such infrastructure is essential for advancing synthetic biology:

“This technology allows us to push the boundaries of what is possible in biomanufacturing.”

The fundamental design approaches developed through this work hold promise to guide researchers in manipulating both plant and mammalian genomes promoting new synthetic biology potentials. Research conducted to mitigate risks associated with placing disruptive elements near essential genes has created new possibilities for precise genome engineering.

Research published in Nature Communications demonstrates both the successful end of the Sc2.0 project and a transformative stage in synthetic biology fields. The foundation the scientific community has now established will enable them to take on food security and medicine production challenges while developing sustainable manufacturing solutions which ensure a future proof response to global difficulties.

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