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
SC-33.2 Biological Systems Science Division, BER
BER supports basic research and scientific user facilities to advance DOE missions in energy and environment. More about BER
Mar 23, 2021
Molecular Connections from Plants to Fungi to Ants
Lipids transfer energy and serve as an inter-kingdom communication tool in leaf-cutter ants&rsqu [more...]
Mar 19, 2021
Microbes Use Ancient Metabolism to Cycle Phosphorus
Microbial cycling of phosphorus through reduction-oxidation reactions is older and more widespre [more...]
Feb 22, 2021
Warming Soil Means Stronger Microbe Networks
Soil warming leads to more complex, larger, and more connected networks of microbes in those soi [more...]
Jan 27, 2021
Labeling the Thale Cress Metabolites
New data pipeline identifies metabolites following heavy isotope labeling.
Aug 31, 2020
Novel Bacterial Clade Reveals Origin of Form I Rubisco
List all highlights (possible long download time)