In a groundbreaking achievement, scientists have achieved the remarkable feat of creating an entire chromosome from scratch for the very first time. This artificial chromosome, known as the tRNA Neochromosome, has been crafted for the common baker’s yeast Saccharomyces cerevisiae and holds the potential to usher in a new era of synthetic and enhanced yeast cells, as detailed in recent publications in the scientific journals Cell and Cell Genomics.
This achievement is a significant milestone in the international Sc2.0 project, which aims to synthesize all 16 chromosomes of the yeast and eventually assemble them into a fully functional cell. The ultimate goal is to enhance the yeast’s speed, resilience, and productivity.
The tRNA Neochromosome is a unique creation in that it is entirely synthetic, not derived from any of the yeast’s original chromosomes. Patrick Cai, Chair in Synthetic Genomics at the University of Manchester, international coordinator of the Sc2.0 project, and co-author of the Cell paper, described it as “the world’s first de novo synthetic chromosome.” Unlike the other 16 synthetic chromosomes, the tRNA Neochromosome was not modeled after an existing natural chromosome but was meticulously designed piece by piece using computer-aided techniques, incorporating genetic material from at least nine different microorganisms.
What makes this synthetic chromosome especially remarkable is its ability to function like a natural genome, producing tRNAs, and its design to prevent “head-on collisions” between RNA polymerase and DNA polymerase, which can lead to DNA damage and other cellular challenges.
Currently, six and a half of the synthetic chromosomes have been successfully combined within a yeast cell as part of the Sc2.0 project. The hope is that these synthetic yeast cells will operate more efficiently, yield better results, and exhibit greater resilience in the face of environmental changes. They could find applications in the production of bread, biofuels, pharmaceuticals, flavors, and fragrances.
Cai emphasized that these synthetic yeast cells behave similarly to natural cells under standard conditions but can transform into “super-yeast” when faced with challenging conditions like high temperatures or extreme pH levels. These synthetic chromosomes have been endowed with new functions that allow them to adapt to different environments as needed.
The creation of the tRNA Neochromosome was aided by artificial intelligence, incorporating genes from other organisms to optimize yeast qualities. This synthetic chromosome will eventually be integrated into the synthetic yeast cells.
Cai explained the process: “We designed these synthetic chromosomes using computer-assisted designers, similar to those used for designing buildings and cars. Then, we synthesized these synthetic chromosomes piece by piece within the cell, replacing wild-type sequences, much like rewriting a chapter of a book paragraph by paragraph until a new chapter emerges. Now, all 16 chromosomes are complete, bringing us one step closer to deciphering the ultimate code of life.”
This research holds promise beyond yeast cells and may one day be applicable to humans, potentially opening doors to genetic mutation manipulation and gene therapies. Cai stated, “This will have a significant impact on human health, allowing us to directly test driver mutations for diseases and paving the way for improved gene therapies.”
Researchers are now working towards completing the final Sc2.0 strain, which will include all the synthetic yeast chromosomes and the tRNA Neochromosome, marking the creation of the first synthetic eukaryote ever. Cai noted that these synthetic yeast cells offer new insights into how genomes could be organized and deepen our understanding of the fundamental principles of life.