Optimizing Yeast For Xylose Fermentation Through Systems Biology

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With the rise of fossil fuel prices and our growing concerned over the health impacts of poor air quality, greenhouse gas emission and climate change, increasingly we are looking to renewable alternative energy sources such as ethanol. Presently the majority of the world's ethanol is produced by the fermentation of sugarcane or corn. However cellulosic fermentation has many advantages as cellulose, the main component of plant cell walls, is plentiful in agricultural and forestry waste and does not compete with food sources. Unfortunately, numerous hurdles remain in making cellulosic ethanol production a commercially viable industry. One problem is the yeast we have been using to make alcohol for 1000s of years, though outstandingly efficient at making alcohol from simple sugars like glucose found in grains and grapes, are inefficient at making alcohol from complex sugars such as xylose. As a significant percentage of the sugar content of cellulose is xylose, it is essential to optimize xylose fermentation in yeast. Traditionally, to address this issue genes with known roles in xylose utilization from other species have been incorporated into yeast; however xylose fermentation is still inefficient. In contrast to taking a "directed" approach, which is limited by our present state of knowledge of the genes regulating xylose fermentation, the Baetz lab has recently taken a global approach where we systematically screened nearly every gene in yeast to see if removing a gene had negative or positive impact on xylose fermentation. Surprisingly, we found that the removal or deletion of four genes, with no known connection to xylose metabolism, dramatically improved yeast's ability to ferment xylose. This illustrates the power of performing un-biased global or genome-wide screens. The aim of this proposal is to extend our genome-wide studies to understand how the deletion of these four genes results in efficient xylose fermentation and to further characterize the genes regulating yeast's natural ability to ferment xylose. Our overall goal will be to engineer these genes to maximize ethanol production from xylose, which will aid the cellulosic biofuels industry in Canada.