In a groundbreaking achievement, scientists from the NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), the Synthetic Biology Translational Research Program (Syn Bio TRP), and the Department of Biochemistry at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), have successfully synthesized Chromosome XV of yeast, encompassing 1.05 million base pairs. This marks a major milestone in synthetic biology and is the largest synthesized chromosome in Asia.
Published in Cell Genomics, the research is part of the Synthetic Yeast Genome Project (Sc2.0), an international consortium aiming to redesign and construct all 16 yeast chromosomes. Led by Associate Professor Matthew Chang, the NUS Medicine team employed innovative technology, CRISPR/Cas9-mediated mitotic recombination with endoreduplication (CRIMiRE), to streamline the assembly process of synXV.
CRIMiRE significantly accelerates the exchange of large chromosomal DNA segments at specific sites, allowing multiple synthetic chromosome segments to be assembled simultaneously and stitched together into a complete synthetic Chromosome XV. This groundbreaking technology also enables intentional mixing and matching of synXV with another yeast chromosome, generating diverse genetic combinations for studies on the link between genetic variations and individual traits.
The synthetic yeast chromosome, created with CRIMiRE, addresses the challenges of working with extremely long DNA sequences. Traditional approaches are often inefficient in changing sequences, but CRIMiRE has revolutionized the process, shortening it tenfold.
Associate Professor Matthew Chang emphasized, "This achievement opens the door to understanding basic questions about biological processes. Our journey to complete the construction of the synthetic yeast chromosome has been remarkable, showcasing technical prowess and offering the potential for groundbreaking advancements that can ultimately benefit humanity."
Dr. Foo Jee Loon, Research Assistant Professor from SynCTI, Syn Bio TRP, and the Department of Biochemistry at NUS Medicine, the first author of the paper, highlighted the promise of this work in advancing synthetic genomics, especially with larger and more complex chromosomes. The approach holds potential in deciphering the mechanisms of genetic diseases and devising treatments. The study's success paves the way for future breakthroughs in synthetic biology and genomic research.
