Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica
Abstract
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.
- Authors:
-
[1];
[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
- Publication Date:
- Research Org.:
- 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 Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); Novo Nordisk Foundation
- OSTI Identifier:
- 1624016
- Alternate Identifier(s):
- OSTI ID: 1768026
- Report Number(s):
- PNNL-SA-111282
Journal ID: ISSN 2056-7189; PII: BFnpjsba20165
- Grant/Contract Number:
- SC0008744; AC05-76RL01830
- Resource Type:
- Accepted Manuscript
- Journal Name:
- npj Systems Biology and Applications
- Additional Journal Information:
- Journal Volume: 2; Journal Issue: 1; Journal ID: ISSN 2056-7189
- Publisher:
- Springer Nature
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; biotechnology; metabolic engineering; microbiology; systems analysis; yarrowia lipolytica; lipid; chemostat
Citation Formats
Kerkhoven, Eduard J., Pomraning, Kyle R., Baker, Scott E., and Nielsen, Jens. Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica. United States: N. p., 2016.
Web. doi:10.1038/npjsba.2016.5.
Kerkhoven, Eduard J., Pomraning, Kyle R., Baker, Scott E., & Nielsen, Jens. Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica. United States. https://doi.org/10.1038/npjsba.2016.5
Kerkhoven, Eduard J., Pomraning, Kyle R., Baker, Scott E., and Nielsen, Jens. Thu .
"Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica". United States. https://doi.org/10.1038/npjsba.2016.5. https://www.osti.gov/servlets/purl/1624016.
@article{osti_1624016,
title = {Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica},
author = {Kerkhoven, Eduard J. and Pomraning, Kyle R. and Baker, Scott E. and Nielsen, Jens},
abstractNote = {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.},
doi = {10.1038/npjsba.2016.5},
journal = {npj Systems Biology and Applications},
number = 1,
volume = 2,
place = {United States},
year = {Thu Mar 03 00:00:00 EST 2016},
month = {Thu Mar 03 00:00:00 EST 2016}
}
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