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Biological Chemistry

First Total Synthesis Of Eukaryote Chromosome Achieved

Synthetic Biology: Altered brewer’s yeast thrives with artificial genetic material, holds promise for entire designer genomes

by Elizabeth K. Wilson
March 31, 2014 | A version of this story appeared in Volume 92, Issue 13

Credit: Lucy Reading-Ikkanda
An artificial yeast chromosome contains numerous alterations (colored pins and white dots) and deletions (yellow segments).
Model of a yeast chromosome.
Credit: Lucy Reading-Ikkanda
An artificial yeast chromosome contains numerous alterations (colored pins and white dots) and deletions (yellow segments).

In a significant breakthrough for biological engineering, scientists have created an artificial eukaryote chromosome and inserted it into living brewer’s yeast cells (Science 2014, DOI: 10.1126/science.1249252 ).

The work carries implications beyond that of engineering organisms that can produce biofuels or better beer. Scientists now have within their sights the synthesis of an entire eukaryote genome.

A large international group led by Jef D. Boeke, director of the Institute for Systems Genetics at New York University, and Srinivasan Chandrasegaran, environmental health sciences professor at Johns Hopkins University, designed a variant of chromosome III of Saccharomyces cerevisiae. They were able to alter the yeast’s growth patterns by further changing the artificial chromosome, which they call synIII.

“This work is another remarkable example of how synthetic biology can be used to rewrite chromosome sequences at a sizable scale,” a group including bioengineering pioneer J. Craig Venter of the J. Craig Venter Institute told C&EN.

Biological engineers have already made much progress in altering and synthesizing bacterial chromosomes and viral DNA. But these organisms are prokaryotes, whose single loop of DNA floats in a soup of cytoplasm.

Yeast belongs to the eukaryote branch of life, which includes all plants, animals, and fungi. Eukaryotic cells have distinct nuclei, and their DNA is organized into chromosomes. Eukaryote chromosomes also contain a great deal of “junk” DNA—regions that don’t code for proteins but are increasingly seen to be involved in gene regulation. The team wanted to see how much genetic tweaking a yeast cell could withstand and still survive.

The yeast’s native chromosome III has 319,667 base pairs. Using computational methods, the team made more than 500 changes to the chromosome. They stripped it down to 273,871 base pairs, eliminating repeating sections. They found that yeast cells with synIII behaved normally. They also incorporated a “genome scrambling system” to alter the chromosome and give the cells new properties. With this strategy, they hope to boost yeast’s production of materials, such as alcohol and other biofuels.

“Our research moves the needle in synthetic biology from theory to reality,” Boeke says.


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