Macquarie University researchers, in collaboration with an international team, have completed the creation of the final chromosome in the world's first synthetic yeast genome. This achievement marks a significant milestone in the global Sc2.0 project aimed at constructing a synthetic eukaryotic genome from Saccharomyces cerevisiae (baker's yeast) and a new-to-nature tRNA neochromosome.
Utilizing advanced genome-editing techniques, including the CRISPR D-BUGS protocol, the team identified and rectified genetic errors affecting yeast growth. These corrections restored the strain's capability to grow on glycerol, a vital carbon source, under elevated temperatures.
The findings, published in Nature Communications, showcase how engineered chromosomes can be designed, constructed, and debugged to create more resilient organisms, potentially securing supply chains for food and medicine amid climate change and future pandemics.
Professor Sakkie Pretorius, Co-Chief Investigator and Deputy Vice Chancellor (Research) at Macquarie University, stated, "This is a landmark moment in synthetic biology. It is the final piece of a puzzle that has occupied synthetic biology researchers for many years now." Distinguished Professor Ian Paulsen, Director of the ARC Centre of Excellence in Synthetic Biology, emphasized that the successful construction of the final synthetic chromosome completes a robust platform for engineering biology, which could revolutionize the production of medicines and sustainable materials.
The research team employed specialized gene editing tools to diagnose and rectify issues in the synthetic chromosome that hindered yeast reproduction and growth under challenging conditions. They found that the positioning of genetic markers near uncertain gene regions inadvertently disrupted the activation of essential genes, particularly affecting processes like copper metabolism and cell division.
Co-lead author Dr. Hugh Goold from The NSW Department of Primary Industries remarked, "One of our key findings was how the positioning of genetic markers could disrupt the expression of essential genes. This discovery has important implications for future genome engineering projects, aiding in establishing design principles applicable to other organisms."
The completion of the chromosome known as synXVI allows for new explorations in metabolic engineering and strain optimization. The synthetic chromosome possesses features enabling researchers to generate genetic diversity on demand, expediting the development of yeasts with enhanced capabilities for biotechnology applications.
Dr. Briardo Llorente, Chief Scientific Officer at the Australian Genome Foundry, noted, "The synthetic yeast genome represents a quantum leap in our ability to engineer biology." The construction of such a large synthetic chromosome was facilitated by robotic instrumentation at the Australian Genome Foundry, paving the way for more efficient and sustainable biomanufacturing processes, from pharmaceuticals to new materials.
The research provides valuable insights for future synthetic biology projects, including potential applications in engineering plant and mammalian genomes. The team's design principles for synthetic chromosomes will assist other researchers in avoiding disruptive genetic elements near critical genes.