Can engineering protein subcellular localization protect yeast cells from toxic fermentation inhibitors?

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The Bioeconomy is one of Canada's fast growing sectors. Bioproducts, including biofuels, biochemical and biomaterials, are renewable products generated from biomass such as agricultural, forestry, aquaculture and even garbage. This is largely done through conversion of biomass into bioproducts using microorganism-based fermentation, similar to yeast converting grapes to wine. Statistics Canada's 2015 Bioproducts Production and Development Survey indicate that 190 Canadian companies were manufacturing bioproducts with an estimated sales of $4.3 billion, up from $1.3 Billion in in 2009. Despite a fast growing Bioeconomy, major challenges remain.******The emerging industry has turned towards lignocellulosic biomass found in agricultural and forestry waste, as well as energy crops such as grasses grown on marginal lands. The bioconversion of lignocellulose is a two-step process involving the hydrolysis or breaking down of the biomass into mixed sugars that are then converted to bioproducts by fermentation by microorganisms like yeast. However, in addition to the release of sugars, the hydrolysis step also generates a complex mix of toxic compounds that severely inhibit yeast growth and fermentation. One of the greatest challenges for yeast-based bioproduct industry is the development of yeast that can survive in the toxic mix of chemicals found in lignocellulosic hydrolysates. Simple put, yeast cannot ferment if they are dead. ******My research program exploits a variety of cutting-edge genome-wide or “OMICs” technologies to discover the mechanisms by which both individual and complex mixtures of hydrolysate toxins kill yeast. Recently we made the surprising discovery that some proteins change location within the cell upon exposure to a toxin and that this change of protein location may help protect the cell from the toxins. Our work has lead us to ask if we can exploit protein localization to increase resistance to hydrolysate toxins and ultimately improve bioproduct production. The goal of this research program is to identify proteins that change location within the cell upon toxin exposure, identify how and why they change location, including if the change in location offers protection from toxins. Our study will be the first to assess the potential of engineering protein subcellular localization to improve toxin tolerance on a large scale and may lead to groundbreaking advances in the development of industrial yeast. ******This grant will also address another major hurdle of the Bioproduct Industry, the availability of highly trained personal. Presently over 1000 people are employed in R&D or technicians with in this industry, but 17.1% of companies reported vacant positions due to an inability to find HQP in 2015. This research program will produce HQP with knowledge of state-of-the-art technologies needed for the continued growth of this sector in Canada. **