The field of synthetic biology has reached a historic milestone. Researchers at Macquarie University, in collaboration with an international team, have completed the creation of the final chromosome in the world’s first synthetic eukaryotic genome. This achievement marks the conclusion of the global Sc2.0 project and introduces an entirely new concept: a synthetic tRNA neochromosome.

Using cutting-edge genome-editing techniques, including the CRISPR D-BUGS protocol, the team meticulously identified and corrected genetic errors that had impaired the growth of Saccharomyces cerevisiae—commonly known as baker’s yeast. Their efforts not only restored the yeast’s ability to grow on glycerol, a vital carbon source, under elevated temperatures but also paved the way for engineering more resilient organisms. The findings, published in Nature Communications this week, underscore the power of synthetic chromosomes to tackle real-world challenges such as climate change and global pandemics.

A New Platform for Engineering Life

“This is a landmark moment in synthetic biology,” says Professor Sakkie Pretorius, Co-Chief Investigator and Deputy Vice-Chancellor (Research) of Macquarie University. “It is the final piece of a puzzle that has occupied synthetic biology researchers for many years now.”

The synthetic chromosome, dubbed synXVI, is the crowning achievement of years of global collaboration. Distinguished Professor Ian Paulsen, Director of the ARC Centre of Excellence in Synthetic Biology and co-leader of the project, highlights its transformative potential: “By successfully constructing and debugging the final synthetic chromosome, we’ve helped complete a powerful platform for engineering biology that could revolutionize how we produce medicines, sustainable materials, and other vital resources.”

The team’s meticulous work involved debugging issues that had hindered the yeast’s performance. Using specialized gene-editing tools, they discovered how the placement of genetic markers near uncertain gene regions disrupted crucial processes such as copper metabolism and cell division.

“One of our key findings was how the positioning of genetic markers could disrupt the expression of essential genes,” explains co-lead author Dr. Hugh Goold, research scientist at the NSW Department of Primary Industries and Honorary Postdoctoral Research Fellow at Macquarie University’s School of Natural Sciences. “This discovery has important implications for future genome engineering projects, helping establish design principles that can be applied to other organisms.”

Unlocking Biotech’s Full Potential

The implications of this work are vast. The completed synthetic genome provides a launchpad for metabolic engineering and strain optimization, making it possible to accelerate the development of yeasts with enhanced capabilities for a range of biotechnology applications.

“The synthetic yeast genome represents a quantum leap in our ability to engineer biology,” says Dr. Briardo Llorente, Chief Scientific Officer at the Australian Genome Foundry. “This achievement opens up exciting possibilities for developing more efficient and sustainable biomanufacturing processes, from producing pharmaceuticals to creating new materials.”

This achievement would not have been possible without the robotic instrumentation at the Australian Genome Foundry. The creation of the large synthetic chromosome serves as a template for future work, including engineering plant and mammalian genomes. The team’s insights into avoiding disruptive genetic elements near critical genes will guide researchers in future synthetic biology projects.

As the world faces mounting challenges, from climate change to pandemics, synthetic biology is emerging as a powerful tool. The completion of the first synthetic yeast genome not only exemplifies human ingenuity but also signals a new era in bioengineering. The possibilities are just beginning.