Dataset Information

Kavšček2015 - Genome-scale metabolic model of Yarrowia lipolytica (iMK735)

ABSTRACT: Kavšček2015 - Genome-scale metabolic model of Yarrowia lipolytica (iMK735) This model is described in the article: Optimization of lipid production with a genome-scale model of Yarrowia lipolytica. Kavšček M, Bhutada G, Madl T, Natter K. BMC Syst Biol 2015; 9: 72 Abstract: Yarrowia lipolytica is a non-conventional yeast that is extensively investigated for its ability to excrete citrate or to accumulate large amounts of storage lipids, which is of great significance for single cell oil production. Both traits are thus of interest for basic research as well as for biotechnological applications but they typically occur simultaneously thus lowering the respective yields. Therefore, engineering of strains with high lipid content relies on novel concepts such as computational simulation to better understand the two competing processes and to eliminate citrate excretion.Using a genome-scale model (GSM) of baker's yeast as a scaffold, we reconstructed the metabolic network of Y. lipolytica and optimized it for use in flux balance analysis (FBA), with the aim to simulate growth and lipid production phases of this yeast. We validated our model and found the predictions of the growth behavior of Y. lipolytica in excellent agreement with experimental data. Based on these data, we successfully designed a fed-batch strategy to avoid citrate excretion during the lipid production phase. Further analysis of the network suggested that the oxygen demand of Y. lipolytica is reduced upon induction of lipid synthesis. According to this finding we hypothesized that a reduced aeration rate might induce lipid accumulation. This prediction was indeed confirmed experimentally. In a fermentation combining these two strategies lipid content of the biomass was increased by 80%, and lipid yield was improved more than four-fold, compared to standard conditions.Genome scale network reconstructions provide a powerful tool to predict the effects of genetic modifications and the metabolic response to environmental conditions. The high accuracy and the predictive value of a newly reconstructed GSM of Y. lipolytica to optimize growth conditions for lipid accumulation are demonstrated. Based on these findings, further strategies for engineering Y. lipolytica towards higher efficiency in single cell oil production are discussed. This model is hosted on BioModels Database and identified by: MODEL1510060001. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Nicolas Rodriguez

PROVIDER: MODEL1510060001 | BioModels | 2016-01-20

REPOSITORIES: BioModels

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			Action	DRS
	MODEL1510060001?filename=MODEL1510060001-biopax2.owl	Owl
	MODEL1510060001?filename=MODEL1510060001-biopax3.owl	Owl
	MODEL1510060001?filename=MODEL1510060001.m	Other
	MODEL1510060001?filename=MODEL1510060001.pdf	Pdf
	MODEL1510060001?filename=MODEL1510060001.png	Other

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Publications

Optimization of lipid production with a genome-scale model of Yarrowia lipolytica.

Kavšček Martin M Bhutada Govindprasad G Madl Tobias T Natter Klaus K

BMC systems biology 20151026

<h4>Background</h4>Yarrowia lipolytica is a non-conventional yeast that is extensively investigated for its ability to excrete citrate or to accumulate large amounts of storage lipids, which is of great significance for single cell oil production. Both traits are thus of interest for basic research as well as for biotechnological applications but they typically occur simultaneously thus lowering the respective yields. Therefore, engineering of strains with high lipid content relies on novel conc ...[more]

PMID: 26503450

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Project description:This model is from the article: A genome-scale metabolic model of the lipid-accumulating yeast Yarrowia lipolytica Nicolas Loira, Thierry Dulermo, Jean-Marc Nicaud and David J Sherman BMC Systems Biology 2012, 6:35 doi: 10.1186/1752-0509-6-35 , Abstract: Background Yarrowia lipolytica is an oleaginous yeast which has emerged as an important microorganism for several biotechnological processes, such as the production of organic acids, lipases and proteases. It is also considered a good candidate for single-cell oil production. Although some of its metabolic pathways are well studied, its metabolic engineering is hindered by the lack of a genome-scale model that integrates the current knowledge about its metabolism. Results Combining in silico tools and expert manual curation, we have produced an accurate genome-scale metabolic model for Y. lipolytica. Using a scaffold derived from a functional metabolic model of the well-studied but phylogenetically distant yeast S. cerevisiae, we mapped conserved reactions, rewrote gene associations, added species-specific reactions and inflected specialized copies of scaffold reactions to account for species-specific expansion of protein families. We used physiological measures obtained under lab conditions to validate our predictions. Conclusions Y. lipolytica iNL895represents the first well-annotated metabolic model of an oleaginous yeast, providing a reference for future metabolic improvement, and a starting point for the metabolic reconstruction of other species in the Yarrowia clade and other oleaginous yeasts. Note: This SBML representation of the Yarrowia lipolytica metabolic network is made available under the Creative Commons Attribution-Share Alike 3.0 Unported Licence (see www.creativecommons.org). Nicolas Loira (loira@inria.fr, nloira@gmail.com); based on S.cerevisiae model yeast_4.36.xml (Herrgard, 2008)