Dataset Information

Comprehensive Metabolomic, Lipidomic and Microscopic Profiling of Yarrowia lipolytica during Lipid Accumulation Identifies Targets for Increased Lipogenesis.

ABSTRACT: Yarrowia lipolytica is an oleaginous ascomycete yeast that accumulates large amounts of lipids and has potential as a biofuel producing organism. Despite a growing scientific literature focused on lipid production by Y. lipolytica, there remain significant knowledge gaps regarding the key biological processes involved. We applied a combination of metabolomic and lipidomic profiling approaches as well as microscopic techniques to identify and characterize the key pathways involved in de novo lipid accumulation from glucose in batch cultured, wild-type Y. lipolytica. We found that lipids accumulated rapidly and peaked at 48 hours during the five day experiment, concurrent with a shift in amino acid metabolism. We also report that exhaustion of extracellular sugars coincided with thickening of the cell wall, suggesting that genes involved in cell wall biogenesis may be a useful target for improving the efficiency of lipid producing yeast strains.

SUBMITTER: Pomraning KR

PROVIDER: S-EPMC4408067 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Comprehensive Metabolomic, Lipidomic and Microscopic Profiling of Yarrowia lipolytica during Lipid Accumulation Identifies Targets for Increased Lipogenesis.

Pomraning Kyle R KR Wei Siwei S Karagiosis Sue A SA Kim Young-Mo YM Dohnalkova Alice C AC Arey Bruce W BW Bredeweg Erin L EL Orr Galya G Metz Thomas O TO Baker Scott E SE

PloS one 20150423 4

Yarrowia lipolytica is an oleaginous ascomycete yeast that accumulates large amounts of lipids and has potential as a biofuel producing organism. Despite a growing scientific literature focused on lipid production by Y. lipolytica, there remain significant knowledge gaps regarding the key biological processes involved. We applied a combination of metabolomic and lipidomic profiling approaches as well as microscopic techniques to identify and characterize the key pathways involved in de novo lipi ...[more]

PMID: 25905710

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Project description:The yeast Yarrowia lipolytica is a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis in Y. lipolytica and identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1) with a control strain grown under either nitrogen or carbon limitation conditions. A strong correlation was observed between the responses on the transcript and protein levels. Combination of DGA1 overexpression with nitrogen limitation resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor.IMPORTANCE The ubiquitous metabolism of lipids involves refined regulation, and an enriched understanding of this regulation would have wide implications. Various factors can influence lipid metabolism, including the environment and genetics. We demonstrated, using a multi-omics and multifactorial experimental setup, that multiple factors affect lipid accumulation in the yeast Yarrowia lipolytica Using integrative analysis, we identified novel interactions between nutrient restriction and genetic factors involving regulators that are highly conserved among eukaryotes. Given that lipid metabolism is involved in many diseases but is also vital to the development of microbial cell factories that can provide us with sustainable fuels and oleochemicals, we envision that our report introduces foundational work to further unravel the regulation of lipid accumulation in eukaryal cells.

Dataset Information

Comprehensive Metabolomic, Lipidomic and Microscopic Profiling of Yarrowia lipolytica during Lipid Accumulation Identifies Targets for Increased Lipogenesis.

Publications

Comprehensive Metabolomic, Lipidomic and Microscopic Profiling of Yarrowia lipolytica during Lipid Accumulation Identifies Targets for Increased Lipogenesis.

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