A foundational platform to engineer synthetic heterotrophy in yeast

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Baker's yeast is an important organism for producing ethanol and complex bioproducts, but it can use only a limited number of carbon sources. A variety of renewable and/or cheap carbon sources are currently available. Expanding the capacity of baker's yeast to use these sources to produce bioproducts would be beneficial. The investigators will attempt to discover the mechanisms that control carbon utilization in yeast. Design principles will then be developed to help expand the range of carbon sources that can be used. This will expand the production of renewable fuels and chemicals. Graduate and undergraduate students will participate in this research. They will also be engaged in community outreach efforts to enhance the visibility of the work to the larger community. Non-native substrates represent a significant fraction of renewable and inexpensive feedstocks. Little work has been done to explore the benefits of integrating cellular regulatory control over heterologous assimilation pathways. Therefore, goal of this work is to 1) demonstrate that cellular decision-making when used to couple growth-related processes with non-native substrate assimilation has significant benefits in generating strains of baker?s yeast that can rapidly grow on any number of structurally diverse substrates, and 2) that these insights can be leveraged to develop a universal platform to engineer and optimize growth on non-native substrates. The platform developed here will also enable functional genomics studies to identify modulators of non-native substrate metabolism in a manner not possible in the past. It is anticipated that the outcomes from the project will extend beyond baker's yeast and the substrates that are the focus of this project since the paradigm developed here is expected to aid similar efforts with other industrially relevant microbes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.