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Comparison and Analysis of Published Genome-scale Metabolic Models of Yarrowia lipolytica

  • Research Paper
  • Metabolic Engineering
  • Published:
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Abstract

Background

Genome-scale metabolic models (GEMs) are powerful tools for predicting metabolic flux distributions, understanding complex cell physiology, and guiding the improvement of cell metabolism and production. Yarrowia lipolytica is known for its ability to accumulate lipids and has been widely employed to produce many important metabolites as an ideal host microorganism. There are six GEMs reconstructed for this strain by different research groups, which, however, may cause confusion for model users. It is therefore necessary to understand and analyze the existing models comprehensively.

Results

Different simulation results of the published GEMs of Y. lipolytica were analyzed based on experimental data, in order to understand the differences among models and identify whether there were common problems in model construction. First, specific growth rates (μ) under various culture conditions were simulated by different models, showing that the biomass generation equation in models had significant influence on the accuracy of simulation results. In addition, simulation and analysis of intracellular flux distributions revealed several inaccurate descriptions on the reversibility of reactions involving currency metabolites in the models. Finally, specific metabolite formation rates were predicted for different target products, and large discrepancies among the different models were observed. The corresponding solutions were then proposed according to the findings of the above model problems.

Conclusions

We have corrected the existing GEMs of Y. lipolytica and the prediction performances of the models have been significantly improved. Several suggestions for better construction and refinement of genome-scale metabolic network models were also provided.

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Acknowledgements

We thank Prof. Dong-Yup Lee for providing iYLI647, Prof. Jens Nielsen for providing iYali4, Prof. Klaus Natter for providing iMK735 and Prof. David James Sherman for providing iNL895. We also thank Prof. Joerg M. Buescher for providing the modelBorgifier toolbox and Prof. Sameereh Hashemi-Najafabadi for the BiKEGG toolbox. This study was financially supported by National Natural Science Foundation of China (21776081), National Key R&D Program of China (2017YFE0115600), and the 111 Project (B18022).

The authors declare no conflict of interest.

Neither ethical approval nor informed consent was required for this study.

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Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China

    Yu Xu & Qiang Hua

  2. Institute of Animal Biochemistry and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava, Slovakia

    Roman Holic

  3. Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai, 200237, China

    Qiang Hua

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  1. Yu Xu
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Correspondence to Qiang Hua.

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Xu, Y., Holic, R. & Hua, Q. Comparison and Analysis of Published Genome-scale Metabolic Models of Yarrowia lipolytica. Biotechnol Bioproc E 25, 53–61 (2020). https://doi.org/10.1007/s12257-019-0208-1

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