Rewiring yeast metabolism to synthesize products beyond ethanol |
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| Institution: | 1. Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA;2. DOE Great Lakes Bioenergy Research Center, Univ. of Wisconsin-Madison, USA;3. DOE Center for Advanced Bioenergy and Bioproducts Innovation, Univ. of Wisconsin-Madison, USA;4. Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI, USA;1. Department of Biology and Biological Engineering, Chalmers University of Technology, 41296 Gothenburg, Sweden;2. Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, 41296 Gothenburg, Sweden;3. Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark;1. Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA;2. Energy Biosciences Institute, Berkeley, CA 94720, USA;3. The UC Berkeley & UCSF Graduate Program in Bioengineering, Berkeley, CA 94720, USA;4. Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA;5. Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA |
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| Abstract: | Saccharomyces cerevisiae, Baker's yeast, is the industrial workhorse for producing ethanol and the subject of substantial metabolic engineering research in both industry and academia. S. cerevisiae has been used to demonstrate production of a wide range of chemical products from glucose. However, in many cases, the demonstrations report titers and yields that fall below thresholds for industrial feasibility. Ethanol synthesis is a central part of S. cerevisiae metabolism, and redirecting flux to other products remains a barrier to industrialize strains for producing other molecules. Removing ethanol producing pathways leads to poor fitness, such as impaired growth on glucose. Here, we review metabolic engineering efforts aimed at restoring growth in non-ethanol producing strains with emphasis on relieving glucose repression associated with the Crabtree effect and rewiring metabolism to provide access to critical cellular building blocks. Substantial progress has been made in the past decade, but many opportunities for improvement remain. |
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| Keywords: | Yeast Crabtree–Warburg effect Metabolic engineering Pyruvate decarboxylase deficient Glucose Ethanol Acetyl-CoA Adaptive laboratory evolution |
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