Scientists report completion of chromosome XI, a major step towards creating the world's first synthetic yeast

As part of a significant worldwide endeavor to create the first synthetic yeast genome ever, a group of scientists located in the UK, under the direction of specialists from the Universities of Nottingham and Imperial College London, have finished building a synthetic chromosome.

The UK team's accomplishment, which is part of the largest synthetic biology effort ever—the worldwide synthetic yeast genome collaboration—represents completion of one of the yeast genome's sixteen chromosomes. It was published in Cell Genomics.

Teams from the UK, US, China, Singapore, UK, France, and Australia have been working together for 15 years on a project known as "Sc2.0" to create synthetic replicas of every chromosome in yeast. In addition to this work, nine more publications detailing the chromosomes that other teams have created have also been published. It is anticipated that the genome project, which is the biggest synthetic genome ever, would be completed in 2024.

The creation of a synthetic genome for a eukaryote—a living being with a nucleus, including plants, animals, and fungi—has never been done before. The chosen organism for the endeavor was yeast because of its comparatively small genome and natural capacity to join DNA, which allowed the researchers to create artificial chromosomes inside the yeast cells.

Yeast has a long history with humans; over thousands of years, we domesticated it for baking and brewing, and more recently, we used it to produce chemicals and as a model organism to understand how our own cells function. Because of this link, yeast's genetics is more understood than that of any other creature. Yeast was the apparent choice because of these qualities.

The UK-based team, headed by Professor Tom Ellis of Imperial College London and Dr. Ben Blount of the University of Nottingham, has recently stated that their chromosome, synthetic chromosome XI, has been completed. The chromosomal construction process took ten years, and the resulting DNA sequence, which is made up of base pairs, or the "letters" that make up the DNA code, is about 660,000 in length.

After a laborious debugging procedure, the synthetic chromosome that substituted one of the natural chromosomes in a yeast cell allowed the cell to thrive with the same fitness level as a natural cell. The synthetic genome will have several uses in addition to assisting scientists in their understanding of how genomes work.

The Sc2.0 synthetic genome has been constructed with additional traits that provide cells unique skills not present in nature, rather than being a direct clone of the natural genome. Thanks to one of these qualities, scientists can make millions of distinct cell variants with varying properties by forcing the cells to shuffle their gene content. Then, individuals with better qualities can be chosen for a variety of uses in biotechnology, bioenergy, and medicine. In essence, the procedure is supercharged evolution.

Moreover, the group has demonstrated that their chromosome may be repurposed as a novel tool for the investigation of extrachromosomal circular DNAs, or eccDNAs. These are free-floating DNA circles that have "looped out" of the genome and are being identified more and more as aging factors, causes of malignant development, and a role in the resistance to chemotherapy that many malignancies, including brain tumors from glioblastoma, have to these drugs.

One of the project's principal scientists, Dr. Ben Blount, is an assistant professor in the University of Nottingham's School of Life Sciences. "The synthetic chromosomes are massive technical achievements in and of themselves, but they will also unleash a plethora of new possibilities for the study and application of biology," he declared. This can involve developing novel microbial strains for more environmentally friendly bioproduction or assisting in the research and treatment of illness."

"The synthetic yeast genome project is an amazing illustration of large-scale science accomplished by a global consortium of researchers. Being a part of such a massive endeavor where everyone engaged was working toward the same common objective has been an amazing experience."

"By constructing a redesigned chromosome from telomere to telomere, and showing it can replace a natural chromosome just fine," said Professor Tom Ellis of the Imperial College London's Center for Synthetic Biology and Department of Bioengineering, "our team's work establishes the foundations for designing and making synthetic chromosomes and even genomes for complex organisms like plants and animals."

The UK team comprises scientists from the universities of Edinburgh, Cambridge, and Manchester in the UK, John Hopkins University and New York University Langone Health in the U.S., and Universidad Nacional Autónoma de México, Querétaro in Mexico, in addition to the leads from Nottingham and Imperial College London.