title: Surveying the lipogenesis landscape in Yarrowia lipolytica through understanding the function of a Mga2p regulatory protein mutant.
abstract: Lipogenic organisms represent great starting points for metabolic engineering of oleochemical production. While previous engineering efforts were able to significantly improve lipid production in Yarrowia lipolytica, the lipogenesis landscape, especially with respect to regulatory elements, has not been fully explored. Through a comparative genomics and transcriptomics approach, we identified and validated a mutant mga2 protein that serves as a regulator of desaturase gene expression and potent lipogenesis factor. The resulting strain is enriched in unsaturated fatty acids. Comparing the underlying mechanism of this mutant to other previously engineered strains suggests that creating an imbalance between glycolysis and the TCA cycle can serve as a driving force for lipogenesis when combined with fatty acid catabolism overexpressions. Further comparative transcriptomics analysis revealed both distinct and convergent rewiring associated with these different genotypes. Finally, by combining metabolic engineering targets, it is possible to further engineer a strain containing the mutant mga2 gene to a lipid production titer of 25g/L.
authors.affiliation: McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St., Stop C0400, Austin, TX 78712, USA.
authors.forename: Leqian
authors.initials: L
authors.lastname: Liu
authors.affiliation: McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St., Stop C0400, Austin, TX 78712, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Markham
authors.affiliation: McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St., Stop C0400, Austin, TX 78712, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blazeck
authors.affiliation: McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St., Stop C0400, Austin, TX 78712, USA.
authors.forename: Nijia
authors.initials: N
authors.lastname: Zhou
authors.affiliation: McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St., Stop C0400, Austin, TX 78712, USA.
authors.forename: Dacia
authors.initials: D
authors.lastname: Leon
authors.affiliation: McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St., Stop C0400, Austin, TX 78712, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Otoupal
authors.affiliation: McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St., Stop C0400, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, The University of Texas at Austin, 2500 Speedway Avenue, Austin, TX 78712, USA. Electronic address: halper@che.utexas.edu.
authors.forename: Hal S
authors.initials: HS
authors.lastname: Alper
mesh_terms: D044943:Fatty Acid Desaturases / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D050155:Lipogenesis; D060847:Metabolic Engineering; D050505:Mutant Proteins / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D059467:Transcriptome; D025062:Yarrowia / Q000235:genetics / Q000378:metabolism*
chemical_list: D005231:Fatty Acids, Unsaturated; D005656:Fungal Proteins; D050505:Mutant Proteins; D044943:Fatty Acid Desaturases
keywords: Lipogenesis; Metabolic engineering; Yarrowia; Yeast; mga2