Journal article
Engineering yeast phospholipid metabolism for de novo oleoylethanolamide production
Phospholipids, the most abundant membrane lipid components, are crucial in maintaining membrane structures and homeostasis for biofunctions. As a structurally diverse and tightly regulated system involved in multiple organelles, phospholipid metabolism is complicated to manipulate. Thus, repurposing phospholipids for lipid-derived chemical production remains unexplored.
Herein, we develop a Saccharomyces cerevisiae platform for de novo production of oleoylethanolamide, a phospholipid derivative with promising pharmacological applications in ameliorating lipid dysfunction and neurobehavioral symptoms. Through deregulation of phospholipid metabolism, screening of biosynthetic enzymes, engineering of subcellular trafficking and process optimization, we could produce oleoylethanolamide at a titer of 8,115.7 µg l−1 and a yield on glucose of 405.8 µg g−1.
Our work provides a proof-of-concept study for systemically repurposing phospholipid metabolism for conversion towards value-added biological chemicals, and this multi-faceted framework may shed light on tailoring phospholipid metabolism in other microbial hosts.
Language: | English |
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Publisher: | Nature Publishing Group US |
Year: | 2020 |
Pages: | 197-205 |
ISSN: | 15524469 and 15524450 |
Types: | Journal article |
DOI: | 10.1038/s41589-019-0431-2 |
ORCIDs: | 0000-0002-9955-6003 |
Acyl Coenzyme A CDPdiacylglycerol-Serine O-Phosphatidyltransferase CHO1 protein, S cerevisiae Coenzyme A Ligases Endocannabinoids Enzymes Escherichia coli Proteins FAA4 protein, S cerevisiae Faa1 protein, S cerevisiae Gene Expression Regulation, Fungal Glucose Lysophospholipase Metabolic Engineering Microorganisms, Genetically-Modified Monoacylglycerol Lipases Oleic Acids Periplasmic Proteins Phospholipids Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Yju3 protein, S cerevisiae oleoylethanolamide tesA protein, E coli