After more than a decade of work, researchers have reached a major milestone in their efforts to re-engineer life in the lab, putting together the final chromosome in a synthetic yeast (Saccharomyces cerevisiae) genome.
The researchers, led by a team from Macquarie University in Australia, chose yeast as a way to demonstrate the potential for producing foodstuffs that could survive the rigors of a changing climate or widespread disease.
It’s the first time a synthetic eukaryotic genome has been constructed in full, following on from successes with simpler bacteria organisms. It’s a proof-of-concept for how more complex organisms, like food crops, could be synthesized by scientists.
“This is a landmark moment in synthetic biology,” says molecular microbiologist Sakkie Pretorius, from Macquarie University. “It is the final piece of a puzzle that has occupied synthetic biology researchers for many years now.”
This doesn’t mean we can start growing completely artificial yeast from scratch, but it does mean living yeast cells can potentially be entirely recoded – though lots more work is required to get this process refined and scaled up before that can happen.
And the coding analogy is a good one, because the researchers had to spend plenty of time and effort debugging the 16th and final synthetic yeast chromosome (called SynXVI) before the genome functioned as desired.
A variety of gene-editing tools, such as one based on CRISPR, were deployed to spot and fix problems in the chromosome. For example, they needed to get the yeast to properly use glycerol as an energy source at higher temperatures, which is something that scientists might want to do to improve yeast resilience.
Another issue the team overcame was with genetic markers, used to identify and track DNA inside the genome. The placing of these markers matters, it turns out – getting it wrong can interfere with cell behavior.
“One of our key findings was how the positioning of genetic markers could disrupt the expression of essential genes,” says synthetic biologist Hugh Goold, from Macquarie University.
The Sc2.0 project, of which this research is a part, isn’t just about modifying crops. The same principles could also be applied to medicines and sustainable materials, with opportunities to speed up their production or make them tougher.
Our efforts in genetic engineering continue to get more ambitious and more comprehensive, and this is another significant step down that road. The improvements are in part down to advances in technology and techniques, with the robotics available at the Australian Genome Foundry crucial in this particular study.
“The synthetic yeast genome represents a quantum leap in our ability to engineer biology,” says synthetic biologist Briardo Llorente, from Macquarie University. “This achievement opens up exciting possibilities for developing more efficient and sustainable biomanufacturing processes, from producing pharmaceuticals to creating new materials.”
The research has been published in Nature Communications.
