Scientists are five steps closers to completing an entire synthetic genome for yeast, a microbe commonly used in beer and bread for thousands of years now, and it could pave the way for a breed of new organisms designed by humans.
The international team led by geneticist Dr. Jef Boeke of New York University Langone and composed of more than 200 authors announced last March 9 that they have constructed and integrated five new synthetic chromosomes into Saccharomyces cerevisiae.
Manufacturing Synthetic Genome For Yeast
The project, dubbed Synthetic Yeast 2.0, brought the total of new chromosomes to 6 of yeast’s 16. This proved that more than 30 percent of a key organism’s genetic material can be substituted with artificial code, and researchers are eyeing to reach 100 percent or the entire synthetic one-celled microorganism by the end of 2017.
The mission is a shot at manufacturing the code of life, where scientists rewrite entire genomes instead of doing genetic modifications that change only small amounts of genes at a given time. This way, they could remove excess or unstable genetic regions and add fresh DNA.
The swaths of synthetic DNA are hoped to produce drugs and vaccines, make food more nutritious, or even grow organs for human transplants.
"This work sets the stage for completion of designer, synthetic genomes to address unmet needs in medicine and industry," said Boeke in a statement of their goal to reprogram chromosomes in living cells.
The new series of papers published in the journal Science detailed how the team used computer design on each of the 16 baker’s yeast chromosomes, taking the sequence of Gs, Ts, Cs, and As and applied thousands of changes to remove unnecessary strands.
Next, biotech firms specializing in DNA synthesis assemble short sequences and stitch them together with longer strands and then weaved into longer chunks. Finally, those DNA chunks are integrated into yeast cells and replace the natural chromosome with synthetic ones until it shows the design on the computer.
The synthetic chromosomes are quite leaner than their natural counterparts, and the Sc2.0 genome plan contains about 1 million nucleotide-level differences from the natural version.
What’s The Next Step?
Once all 16 chromosomes have been successfully built, they will be slipped into a single cell to see how they work together. In a yeast strain already designed by postdoctoral fellow Leslie Mitchell and containing three synthetic chromosomes, the system was seen to surprisingly work well.
“One of the mottos of synthetic biology is we hope to fail, because that’s when you learn. So, in a way, our failure rate is almost disappointingly low,” Boeke said in a Discover Magazine report.
Costs remain a challenge in this human endeavor, as the entire yeast genome was worth $1.25 million excluding labor, materials, sequence verification, as well as debugging. What more for constructing more intricate genomes?
The human genome is approximately 300 times the size of the yeast genome, Boeke said, and they target driving down the costs to a point where the DNA is practically free.
Apart from heralding a new era in synthetic biology, genome engineering will open doors for potential applications. In the industrial world, modified yeast already create spider silk, insulin, and painkilling medication, to name a few. Scientists foresee further uses of human-designed organisms in drug production, conversion of waste into energy, and even creating organs for human transplant needs.
Which organisms are up next? Currently being explored are nematode worms, plants, and even mammalian cells, and eventually animals such as pigs could have genomes designed to convert their organs into suitable human transplants.
This coming May, Boeke and the team will conduct a public meeting to broach the idea of creating human genomes to potentially produce human cells for medical treatments, especially the virus-resistant ones.
Last January, scientists announced the development of the first semi-synthetic organism using an expanded genetic code.
Synthesizing a DNA base pair in their 2014 study, they created bacteria that thrive using the expanded “genetic alphabet.” With an additional X and Y for an “unnatural base pair” (UBP), the modified E. coli bacterium maintains a genetic code of six letters.
