New Capabilities for Genome-Wide Engineering of Yeast

by Claudia Lutz (Chemical and Biomolecular Engineering at Illinois) New approach combines synthetic biology, genome editing tools, and automation to quickly and effectively produce novel yeast strains

One of humankind’s oldest industrial partners is yeast, a familiar microbe that enabled early societies to brew beer and leaven bread and empowers modern ones to synthesize biofuels and conduct key biomedical research. Yeast remains a vital biological agent, yet our ability to explore and influence its genomic activity has lagged.

In a new article in Nature Communications (DOI: 10.1038/NCOMMS15187), University of Illinois researchers describe how their successful integration of several cutting-edge technologies—creation of standardized genetic components, implementation of customizable genome editing tools, and large-scale automation of molecular biology laboratory tasks—will enhance our ability to work with yeast. The results of their new method demonstrate its potential to produce valuable novel strains of yeast for industrial use, as well as to reveal a more sophisticated understanding of the yeast genome.

“The goal of the work was really to develop a genome-scale engineering tool for yeast . . . traditional metabolic engineering focused on just a few genes and the few existing genome-scale engineering tools are only applicable to bacteria, not eukaryotic organisms like yeast,” said Steven L. Miller Chair of Chemical and Biomolecular Engineering Huimin Zhao, who led the study. “A second innovation is the use of synthetic biology concepts, the modularization of the parts, and integration with a robotic system, so we can do it in high-throughput.”

The team focused on yeast in part because of its important modern-day applications; yeasts are used to convert the sugars of biomass feedstocks into biofuels such as ethanol and industrial chemicals such as lactic acid, or to break down organic pollutants. Because yeast and other fungi, like humans, are eukaryotes, organisms with a compartmentalized cellular structure and complex mechanisms for control of their gene activity, study of yeast genome function is also a key component of biomedical research.

“The first time we did this, in 2013, there was no CRISPR . . . the best we could get was 1% of the cells modified in one run,” said Si. “We struggled a little on that, and when CRISPR came out, that worked. We got it to 70% [cells modified], so that was very important.” READ MORE