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Engineering of a high lipid producing Yarrowia lipolytica strain

BACKGROUND: Microbial lipids are produced by many oleaginous organisms including the well-characterized yeast Yarrowia lipolytica, which can be engineered for increased lipid yield by up-regulation of the lipid biosynthetic pathway and down-regulation or deletion of competing pathways. RESULTS: We d...

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Detalles Bibliográficos
Autores principales: Friedlander, Jonathan, Tsakraklides, Vasiliki, Kamineni, Annapurna, Greenhagen, Emily H., Consiglio, Andrew L., MacEwen, Kyle, Crabtree, Donald V., Afshar, Jonathan, Nugent, Rebecca L., Hamilton, Maureen A., Joe Shaw, A., South, Colin R., Stephanopoulos, Gregory, Brevnova, Elena E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815080/
https://www.ncbi.nlm.nih.gov/pubmed/27034715
http://dx.doi.org/10.1186/s13068-016-0492-3
Descripción
Sumario:BACKGROUND: Microbial lipids are produced by many oleaginous organisms including the well-characterized yeast Yarrowia lipolytica, which can be engineered for increased lipid yield by up-regulation of the lipid biosynthetic pathway and down-regulation or deletion of competing pathways. RESULTS: We describe a strain engineering strategy centered on diacylglycerol acyltransferase (DGA) gene overexpression that applied combinatorial screening of overexpression and deletion genetic targets to construct a high lipid producing yeast biocatalyst. The resulting strain, NS432, combines overexpression of a heterologous DGA1 enzyme from Rhodosporidium toruloides, a heterlogous DGA2 enzyme from Claviceps purpurea, and deletion of the native TGL3 lipase regulator. These three genetic modifications, selected for their effect on lipid production, enabled a 77 % lipid content and 0.21 g lipid per g glucose yield in batch fermentation. In fed-batch glucose fermentation NS432 produced 85 g/L lipid at a productivity of 0.73 g/L/h. CONCLUSIONS: The yields, productivities, and titers reported in this study may further support the applied goal of cost-effective, large -scale microbial lipid production for use as biofuels and biochemicals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13068-016-0492-3) contains supplementary material, which is available to authorized users.