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Combinatorial Optimization of Succinate Production in Escherichia coli

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Part of the book series: Lecture Notes in Networks and Systems ((LNNS,volume 325))

Abstract

Genome-scale metabolic models are mathematical formulations widely used to describe the relationship between cells’ genotype and phenotype. Over the years, several attempts have been made to expand these formulations with macromolecular expression. Recently, GECKO models proposed the inclusion of enzyme mass constraints to improve phenotype predictions of a yeast genome-scale metabolic model. Taking a step forward, ETFL formulation includes the gene expression machinery, enabling models to compute the entire metabolic and gene expression proteome in a growing cell. These formulations may lead to more biologically accurate predictions and improve the design of new strains. The present work explores the utilization of such models for the optimization of succinate production in Escherichia coli, taken here as a case study to show the potential of using different modeling approaches in strain design applications. All the optimizations were conducted using MEWpy, a recently proposed Metabolic Engineering Framework.

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References

  1. Maia, P., Rocha, M., Rocha, I.: In silico constraint-based strain optimization methods: the quest for optimal cell factories. Microbiol. Mol. Biol. Rev. 80(1), 45–67 (2016)

    Article  Google Scholar 

  2. Rocha, M., Maia, P., Mendes, R., et al.: Natural computation meta-heuristics for the in silico optimization of microbial strains. BMC Bioinform. 9, 499 (2008)

    Article  Google Scholar 

  3. Rocha, I., Maia, P., Evangelista, P., et al.: OptFlux: an open-source software platform for in silico metabolic engineering. BMC Syst. Biol. 4, 45 (2010)

    Article  Google Scholar 

  4. Sanchez, B.J., Zhang, X.-C., Nilsson, A., Lahtvee, P.-J., Kerkhoven, E.J., Nielsen, J.: Improving the phenotype predictions of a yeast genome-scale metabolic model by incorporating enzymatic constraints. Mol. Syst. Biol. 13, 935 (2017)

    Article  Google Scholar 

  5. Bekiaris, P.S., Klamt, S.: Automatic construction of metabolic models with enzyme constraints. BMC Bioinform. 21, 19 (2020)

    Article  Google Scholar 

  6. Salvy, P., Hatzimanikatis, V.: The ETFL formulation allows multi-omics integration in thermodynamics-compliant metabolism and expression models. Nat. Commun. 11, 30 (2020)

    Article  Google Scholar 

  7. Pereira, V., Cruz, F., Rocha, M.: MEWpy: a computational strain optimization workbench in Python. Bioinformatics (2021)

    Google Scholar 

  8. Lin, H., Bennett, G.N., San, K.: Metabolic engineering of aerobic succinate production systems in Escherichia coli to improve process productivity and achieve the maximum theoretical succinate yield. Metab. Eng. 7(2), 116–127 (2005)

    Article  Google Scholar 

  9. Orth, J.D., et al.: A comprehensive genome-scale reconstruction of Escherichia coli metabolism-2011. Mol. Syst. Biol. 7, 535 (2011)

    Article  Google Scholar 

  10. Ederer, M., et al.: An introduction to kinetic, constraint-based and Boolean modeling in systems biology. In: IEEE International Conference on Control Applications 2010, pp. 129–134 (2010)

    Google Scholar 

  11. Shen, F., Sun, R., Yao, J., et al.: OptRAM: in-silico strain design via integrative regulatory-metabolic network modeling. PLoS Comput. Biol. 15, e1006835 (2019)

    Google Scholar 

  12. O’Brien, E.J., Lerman, J.A., Chang, R.L., Hyduke, D.R., Palsson, B.Ø.: Genome-scale models of metabolism and gene expression extend and refine growth phenotype prediction. Mol. Syst. Biol. 9, 693 (2013)

    Article  Google Scholar 

  13. Hamilton, J.J., Dwivedi, V., Reed, J.L.: Quantitative assessment of thermodynamic constraints on the solution space of genome-scale metabolic models. Biophys. J. 105, 512–522 (2013)

    Article  Google Scholar 

  14. Blankschien, M.D., Clomburg, J.M., Gonzalez, R.: Metabolic engineering of Escherichia coli for the production of succinate from glycerol. Metab Eng. 12, 409–419 (2010)

    Article  Google Scholar 

  15. Li, N.: Directed pathway evolution of the glyoxylate shunt in Escherichia coli for improved aerobic succinate production from glycerol. J. Ind. Microbiol. Biotechnol. 40(12), 1461–1475 (2013)

    Article  Google Scholar 

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Acknowledgements

This project has received funding from the European Union’s Horizon 2020 research and innovation programme (grant agreement number 814408).

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Correspondence to Vítor Pereira .

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Pereira, V., Rocha, M. (2022). Combinatorial Optimization of Succinate Production in Escherichia coli. In: Rocha, M., Fdez-Riverola, F., Mohamad, M.S., Casado-Vara, R. (eds) Practical Applications of Computational Biology & Bioinformatics, 15th International Conference (PACBB 2021). PACBB 2021. Lecture Notes in Networks and Systems, vol 325. Springer, Cham. https://doi.org/10.1007/978-3-030-86258-9_16

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