Engineering Saccharomyces cerevisiae fermentative pathways for the production of isobutanol

Background: Finite supplies of petroleum-based fossil fuels, in addition to concerns about carbon emissions and energy security, have driven the search for alternative fuels that can be produced from renewable resources. Butanol, pentanol and their isomers have significant advantages over ethanol as a biofuel and these can be produced by fermentation. Results: We demonstrate that yeast can be engineered to produce isobutanol by fermentation of carbohydrate precursors. This was achieved by increasing flux through the valine biosynthetic pathway in addition to decreasing pyruvate decarboxylase activity and increasing the availability of NADPH. We found no initial improvement in isobutanol production by deleting BAT1, LEU4 and LEU9, genes encoding enzymes predicted to compete with isobutanol synthesis. Conclusion: Yeast has potential as a factory for the production of higher alcohol biofuels; however, substantial engineering will be required to achieve economically viable production levels.