Building chromosomes from scratch may sound like science fiction, but scientists have actually done it and make it work. In an ambitious effort, researchers have created a fully synthesized chromosome for yeast, a common organism found in baking and brewing. A real surprise? After careful fixation of some defects, laboratory-made chromosomes allow the yeast to grow as normal, even under stress, such as caloric and nutritional shortages. This achievement is part of the Synthetic Yeast Genome Project Version 2.0, which explores how custom genes can reshape our understanding of biology and bring powerful new technologies.
Macquarie University researchers, including Professor Isak Pretorius, Professor Ian Paulsen, Dr. Hugh Goold and Dr. Heinrich Kroukamp, as well as teams from Johns Hopkins University and the University of Edinburgh, led the study. The results they shared in Nature Communications describe how they were built and then repaired this synthetic chromosome to help the yeast grow and behave like the original. These improvements are based on early courses on the same project and involve clever new approaches to fine-tune the design and performance of synthetic DNA.
Creating synthetic chromosomes follows a step-by-step approach. Fragments were produced separately in different yeast strains and then bound by mating and mixing natural DNA. Initially, artificial chromosomes cause poor yeast growth, especially at high temperatures (such as when there are high temperatures or food sources). Scientists have used a method that relies on modern gene editing tools, called the DNA-based upgrade of the genomic system to determine which parts of the synthetic chromosome are to solve the cause of the problem. A major problem was found in the genes responsible for moving copper into cells. Changes in regions that control how this gene activates can interfere with the viability of yeast. Another problem comes from genes associated with cell division, in which design changes disrupt their normal function.
Restoring the original control sequence and reintroducing certain auxiliary RNA molecules, called transfer RNA, helps solve growth problems. According to Professor Pretorius, “We identified the critical error by placing the recombinant site near the gene regulatory region, which had unexpected consequences for gene expression and cellular adaptation.” These corrections allow yeast to recover healthy growth even under challenging conditions, making its behavior more like natural stress.
These corrections lead to valuable insights. Many problems are traced to small DNA tags that are too close to the regions that control important genes. The team responded by developing a clean version called Synthetic Chromosome Version 16 Version 2.0. The updated version removes the problematic region, improves gene stop signal, and reduces the number of added DNA tags. These steps help synthesize chromosomes function more effectively and provide scientists with a more reliable model for establishing artificial chromosomes in other organisms.
Committed to gradually improving the process, researchers follow the cycle of design, testing and refining. They found that while yeast can tolerate many changes in its genetic material, certain parts (especially those genes with few external protein-encoding regions and alternatives) have attracted special attention. Adding all missing transfer RNA to a small, separate DNA circle can significantly improve yeast health, especially under stressful growth conditions.
These lessons from synthetic chromosome 16 are now applied to stronger working versions, providing a great example for the scientific community of how to build truly effective artificial chromosomes. These findings may help guide the design of tailored chromosomes, not only yeast, but even more necessary for the design of animals and plants. Ultimately, this improved chromosome design highlights what today’s genetic tools can do and provides a useful roadmap for building stable, effective and innovative complex genetic systems in the future.
Journal Reference
GOOLD HD, KROUKAMP H., ERPF PE et al. “Architectural and iterative redesign Synxvi 903 KB Synthesis Saccharomyces cerevisiae chromosome. “Nature Communications, 2025. Doi:
About the Author
Professor Isak Pretorius is a leading figure in synthetic biology and biotechnology, known for his work in yeast genetics and genomic engineering. Based in Macquarie University, Australia, he plays a central role in the global design and construction of synthetic eukaryotic genomes, including the landmark synthetic yeast genome project. Professor Pretorius has a background in microbiology and a passion for reprogramming biological systems, making a significant contribution to the development of customized genetic tools for industrial and research applications. His leadership bridges basic science and applied innovation, especially in areas such as winemaking, fermentation and bioengineering. He is also recognized for coaching emerging researchers and fostering international collaborations in genome-scale projects.
Professor Ian Paulson He is a famous microbial genomics expert at Macquarie University, and he focuses on environmental applications of systems biology, synthetic biology and microbiology science. His research spans microbial physiology, metabolic networks and biotechnology purposes for genetic engineering. Professor Paulsen is a key factor in the Synthetic Yeast Genome Project, bringing a data-driven approach to understanding and redesigning the microbial genome. His work often integrates computational modeling and functional genomics to address global challenges in sustainability and industrial biotechnology. His strong commitment to interdisciplinary research is recognized for bridging the gap between computational biology and experimental science.
Dr. Hugh Gold is a senior scientist recognized for his expertise in molecular biology and genomic engineering. He is affiliated with the New South Wales Department of Primary Industry and has extensively developed synthetic biology applications in yeast and other microbial systems. As one of the key factors in the design and commissioning of synthetic chromosome XVI, Dr. Goold helped promote the forefront of genome-scale engineering. His work focuses on improving genetic stability, function and performance in synthetic organisms. Dr. Goold’s research has a practical background in applied biology and is often translated into tools and strategies with a wide range of industrial and agricultural relevances, including biosafety and sustainable biotechnology.
Dr. Heinrich Krukamp He is a microbial biotechnologist and is known for his work on synthetic genome construction and cell engineering. Located in Australia, he is associated with Microbiogen and the University of Macquarie, and has contributed to the major efforts to develop synthetic yeast chromosomes. Dr. Kroukamp’s expertise lies in strain development, fermentation optimization and resolution of biological bottlenecks in engineered organisms. In the Synthetic Yeast Genome Project, he played a key role in testing, debugging and perfecting synthetic DNA to ensure robust growth and performance. His research brings molecular design with practical results, which contributes to innovation in areas such as industrial fermentation, renewable biological products and microbial physiology.
