Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica

Kerkhoven, Eduard J.; Pomraning, Kyle R.; Baker, Scott E.; Nielsen, Jens

doi:10.1038/npjsba.2016.5

Title: Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica

Journal Article · Thu Mar 03 00:00:00 EST 2016 · npj Systems Biology and Applications

DOI:https://doi.org/10.1038/npjsba.2016.5· OSTI ID:1624016

^[1]; Pomraning, Kyle R. ^[2]; Baker, Scott E. ^[2];

^[3]

Chalmers Univ. of Technology, Göteborg (Sweden). Dept. of Biology and Biological Engineering. Systems and Synthetic Biology
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab.
Chalmers Univ. of Technology, Göteborg (Sweden). Dept. of Biology and Biological Engineering. Systems and Synthetic Biology; Technical Univ. of Denmark, Hørsholm (Denmark). Novo Nordisk Foundation Center for Biosustainability

Yarrowia lipolytica is a promising microbial cell factory for the production of lipids to be used as fuels and chemicals, but there are few studies on regulation of its metabolism. Here we performed the first integrated data analysis of Y. lipolytica grown in carbon and nitrogen limited chemostat cultures. We first reconstructed a genome-scale metabolic model and used this for integrative analysis of multilevel omics data. Metabolite profiling and lipidomics was used to quantify the cellular physiology, while regulatory changes were measured using RNAseq. Analysis of the data showed that lipid accumulation in Y. lipolytica does not involve transcriptional regulation of lipid metabolism but is associated with regulation of amino-acid biosynthesis, resulting in redirection of carbon flux during nitrogen limitation from amino acids to lipids. Lipid accumulation in Y. lipolytica at nitrogen limitation is similar to the overflow metabolism observed in many other microorganisms, e.g. ethanol production by Sacchromyces cerevisiae at nitrogen limitation.

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Research Organization:: Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Chalmers Univ. of Technology, Göteborg (Sweden); Technical Univ. of Denmark, Hørsholm (Denmark)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); Novo Nordisk Foundation

Grant/Contract Number:: SC0008744; AC05-76RL01830

OSTI ID:: 1624016

Alternate ID(s):: OSTI ID: 1768026

Report Number(s):: PNNL-SA-111282; PII: BFnpjsba20165

Journal Information:: npj Systems Biology and Applications, Vol. 2, Issue 1; ISSN 2056-7189

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 113 works

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59 BASIC BIOLOGICAL SCIENCES
biotechnology
metabolic engineering
microbiology
systems analysis
yarrowia lipolytica
lipid
chemostat

Title: Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica

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