Engineering metabolic pathways and enzyme subcellular localization enables efficient production of fatty acids and other green chemicals.
Using a combination of different genetic engineering strategies, scientists were able to make oleaginous yeasts convert low-value carbon compounds into different fatty acids and alcohols that can be used for diesel-like fuel production and other industrial applications. The high levels of product achieved with this approach bring the development of a yeast biorefinery platform for high-value fuel and oleochemical production closer to reality.
Oleaginous microorganisms, such as Yarrowia lipolytica, have great potential as industrial producers of biofuels and bioproducts due to their high lipid biosynthetic capacity. However, lipid metabolic engineering in eukaryotes is not advanced enough to take advantage of these organisms. This research demonstrates that a deeper understanding of different aspects of lipid metabolism, from genetic regulation to metabolic compartmentalization to enzyme structure, enables the design and engineering of new strains to substantially increase lipid production.
Researchers at the Massachusetts Institute of Technology applied a multipronged strategy to engineer Y. lipolytica to produce several lipid molecules with applications as biofuels and other oleochemicals such as fatty acid ethyl esters, fatty alkanes, fatty acids, fatty alcohols, and triacylglycerides. This strategy included engineering Y. lipolytica lipid metabolism by expressing enzymes from other microorganisms within specific subcellular compartments within the yeast cells where specific lipids or their precursors are metabolized. Another approach was to engineer a chimeric enzyme to regulate the chain length of specific fatty acids. Finally, to increase the availability of acetyl-CoA building blocks for fatty acid synthesis, alternative acetyl-CoA pathways were designed to avoid the normal repression of acetyl-CoA synthesis by low nitrogen concentration in the medium. Production of different lipid molecules in these engineered strains was increased between 2 and 20 fold, paving the way toward developing industrial strains for commercial production of biodiesel and bioproducts from renewable sources.
Contacts (BER PM)
Office of Biological and Environmental Research
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, Genomic Science program (award DE-SC0008744).
P. Xu, K. Qiao, W. S. Ahn, and G. Stephanopoulos, “Engineering Yarrowia lipolytica as a platform for synthesis of drop-in transportation fuels and oleochemicals.” Proceedings of the National Academy of Sciences (USA) 113(39), 10848-853 (2016). [DOI: 10.1073/pnas.1607295113] (Reference link)
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