Redox metabolism was engineered in Yarrowia lipolytica to increase the availability of reducing molecules needed for lipid production.
With the depletion of fossil fuels, biodiesel precursors produced by oleaginous (oil-producing) yeast from renewable carbohydrates are a promising alternative to fossil- and food-crops-derived fuels. However, production yields are still too low to be commercially competitive. In a new study, researchers achieved a 25% improvement in lipid production, relative to existing oil-producing yeast strains, by rewiring the metabolism in a naturally high lipid producing yeast.
Diesel is used to power large vehicles (e.g., trucks) and is a sought after fuel source due to its high fuel efficiency and energy density. Until now, advances in microbial production of biodiesel were not significant enough to make it close to a commercially viable option. The titer, yield, and productivity of oil achieved in an engineered strain of Y. lipolytica using sugar as substrate are now close to those required to make microbial carbohydrate conversion into fuels commercially viable.
Researchers at the Massachusetts Institute of Technology used a mathematical model to identify the oil production bottlenecks in the industrial yeast Y. lipolytica. With information provided by the model, they designed several metabolic engineering strategies to increase conversion of surplus NADH (a product of glucose degradation) to NADPH, which is needed for lipid biosynthesis. Of the strategies tested, a combination of two were the most effective in lipid yield improvement. By introducing heterologous yeast and bacterial glyceraldhyde-3-phosphate dehydrogenase (GDP) genes that utilize NADP+ instead of NAD+ w into Y. lipolytica and overexpressing a bacterial malic enzyme (MCE2) in the GDP-expressing strain, an improvement of 25% over previously engineered yeasts was observed. In addition, as the engineered Y. lipolytica required less oxygen, it could be grown at higher density in the bioreactor, further increasing biomass and lipid yields. The redox engineering approach reported in this work could be optimized for converting plant biomass into biofuel precursors and other Department of Energy-relevant bioproducts.
Biological Systems Science Division
Office Biological and Environmental Research
U.S. Department of Energy
Department of Chemical Engineering
Massachusetts Institute of Technology
This work was supported by the U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research under award DE-SC0008744.
K. Qiao, T. M. Wasylenko, K. Zhou, P. Xu, and G. Stephanopoulos, “Lipid production in Yarrowia lipolytica is maximized by engineering cytosolic redox metabolism.” Nature Biotechnology 35, 173 (2017). [DOI: 10.1038/nbt.3763] (Reference link)
MIT Press Release: A step towards renewable diesel
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