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Scientists move closer to building synthetic yeast from scratch

Five more chromosomes assembled, 10 to go

By
2:00pm, March 9, 2017
Saccharomyces cerevisiae yeast

BUDDING STAR  With five more synthetic chromosomes built, scientists are closer to creating a synthetic genome for Saccharomyces cerevisiae yeast (shown).

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Synthetic yeast is on the rise.

Scientists have constructed five more yeast chromosomes from scratch. The new work, reported online March 9 in Science, brings researchers closer to completely lab-built yeast. 

“We’re doing it primarily to learn a little more about how cells are wired,” says geneticist Jef Boeke of the New York University Langone Medical Center. But scientists might also be able to tinker with a synthetic yeast cell more efficiently than a natural one, allowing more precise engineering of everything from antiviral drugs to biofuels.

Boeke was part of a team that reported the first synthetic yeast chromosome in 2014 (SN: 5/3/14, p. 7). Now, several hundred scientists in five countries are working to make all 16 Saccharomyces cerevisiae yeast chromosomes and integrate them into living cells. With six chromosomes finished, Boeke hopes the remaining 10 will be built by the end of 2017.

Each synthetic chromosome is based on one of S. cerevisiae’s, but with tweaks for efficiency. Researchers cut out stretches of DNA that can jump around and cause mutations, as well as parts that code for the same information multiple times.  

When the researchers put chunks of synthetic DNA into yeast cells, the cells swapped out parts of their original DNA for the matching engineered snippets.

Yeast is a eukaryote — it stores its DNA in a nucleus, like human cells do. Eventually, this research could produce synthetic chromosomes for more complicated organisms, Boeke says, but such feats are still far in the future.

Group effort

Researchers at schools in five countries are building all 16 yeast chromosomes. Six are now fully complete, and scientists expect to finish the other 10 by the end of 2017. Black dots denote the chromosome’s centromere, the point where chromatids attach during mitosis.

Yeast chromosome building progress report

Citations

S.M. Richardson et al. Design of a synthetic yeast genome. Science. Published online March 9, 2017. doi: 10.1126/science.aaf4557.

G. Mercy et al. 3D organization of synthetic and scrambled chromosomes. Science. Published online March 9, 2017. doi: 10.1126/science.aaf4597.

L.A. Mitchell et al. Synthesis, debugging, and effects of synthetic chromosome consolidation: synVI and beyond. Science. Published online March 9, 2017. doi: 10.1126/science.aaf4831.

Z-X. Xie et al. “Perfect” designer chromosome V and behavior of a ring derivative. Science. Published online March 9, 2017. doi: 10.1126/science.aaf4704.

Y. Shen et al. Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome. Science. Published online March 9, 2017. doi: 10.1126/science.aaf4791.

Y. Wu et al. Bug mapping and fitness testing of chemically synthesized chromosome X. Science. Published online March 9, 2017. doi: 10.1126/science.aaf4706.

L.M. Zahn and G. Riddihough. Building on nature’s design. Science. Published online March 9, 2017. doi: 10.1126/science.aam9871. 

W. Zhang et al. Engineering the ribosomal DNA in a megabase synthetic chromosome. Science. Published online March 9, 2017. doi: 10.1126/science.aaf3981.

Further Reading

T.H. Saey. First chromosome made synthetically from yeast. Science News. Vol. 185, May 3, 2014, p. 7.

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