Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production.
Economic feasibility of biosynthetic fuel and chemical production hinges upon harnessing metabolism to achieve high titre and yield. Here we report a thorough genotypic and phenotypic optimization of an oleaginous organism to create a strain with significant lipogenesis capability. Specifically, we rewire Yarrowia lipolytica's native metabolism for superior de novo lipogenesis by coupling combinatorial multiplexing of lipogenesis targets with phenotypic induction. We further complete direct conversion of lipid content into biodiesel. Tri-level metabolic control results in saturated cells containing upwards of 90% lipid content and titres exceeding 25 g l(-1) lipids, which represents a 60-fold improvement over parental strain and conditions. Through this rewiring effort, we advance fundamental understanding of lipogenesis, demonstrate non-canonical environmental and intracellular stimuli and uncouple lipogenesis from nitrogen starvation. The high titres and carbon-source independent nature of this lipogenesis in Y. lipolytica highlight the potential of this organism as a platform for efficient oleochemical production.
1] McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St. Stop C0400, Austin, Texas 78712, USA [2].
John
J
Blazeck
1] McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St. Stop C0400, Austin, Texas 78712, USA [2].
Andrew
A
Hill
1] McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St. Stop C0400, Austin, Texas 78712, USA [2].
Leqian
L
Liu
Section of Molecular, Cell and Developmental Biology, The University of Texas at Austin, 1 University Station Stop A6700, Austin, Texas 78712, USA.
Rebecca
R
Knight
McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St. Stop C0400, Austin, Texas 78712, USA.
Jarrett
J
Miller
McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St. Stop C0400, Austin, Texas 78712, USA.
Anny
A
Pan
McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St. Stop C0400, Austin, Texas 78712, USA.
Peter
P
Otoupal
1] McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St. Stop C0400, Austin, Texas 78712, USA [2] Institute for Cellular and Molecular Biology, The University of Texas at Austin, 2500 Speedway Avenue, Austin, Texas 78712, USA.
Hal S
HS
Alper
D056804:Biofuels / Q000382:microbiology*; D002244:Carbon / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005285:Fermentation / Q000187:drug effects; D005453:Fluorescence; D005800:Genes, Fungal; D005818:Genetic Engineering; D023281:Genomics; D005838:Genotype; D007532:Isoleucine / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology; D008055:Lipids / Q000096:biosynthesis*; D050155:Lipogenesis / Q000187:drug effects; D010641:Phenotype; D013025:Glycine max / Q000737:chemistry; D013997:Time Factors; D025062:Yarrowia / Q000187:drug effects / Q000378:metabolism*
D056804:Biofuels; D005227:Fatty Acids; D008055:Lipids; D007532:Isoleucine; D002244:Carbon; D007930:Leucine