Knocking out central metabolism genes to identify new targets and alternating substrates to improve lipid synthesis in Y. lipolytica.

ABSTRACT: Introduction: Systematic gene knockout studies may offer us novel insights on cell metabolism and physiology. Specifically, the lipid accumulation mechanism at the molecular or cellular level is yet to be determined in the oleaginous yeast Y. lipolytica. Methods: Herein, we established ten engineered strains with the knockout of important genes involving in central carbon metabolism, NADPH generation, and fatty acid biosynthetic pathways. Results: Our result showed that NADPH sources for lipogenesis include the OxPP pathway, POM cycle, and a trans-mitochondrial isocitrate-α-oxoglutarate NADPH shuttle in Y. lipolytica. Moreover, we found that knockout of mitochondrial NAD⁺ isocitrate dehydrogenase IDH2 and overexpression of cytosolic NADP^+<

SUBMITTER: Zhu J 

PROVIDER: S-EPMC9880266 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature