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Pathway Selection

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Metabolic Pathway Design

Part of the book series: Learning Materials in Biosciences ((LMB))

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Abstract

Several biosynthetic routes are often discovered when screening for ways of connecting the chemical target to the chassis organism through retrosynthesis. The number of alternative pathways can be very high. Pathway enumeration techniques allow determining the alternatives in a systematic way. In this chapter, we will introduce elementary flux mode analysis as one of the most successful approaches for pathway enumeration. Those enumerated pathways need to be ranked in order to select best candidate pathways to engineer. Pathway selection is a multiobjective optimization problem. Different criteria can be used for pathway selection, among others we will discuss here main factors due to enzyme performance, production capabilities and intermediate metabolite toxicity.

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Notes

  1. 1.

    7 https://github.com/brsynth/rp2paths

  2. 2.

    7 https://absynth.issb.genopole.fr/Bioinformatics/

References

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Further Reading

  • Hypergraph techniques for metabolic pathway enumeration:

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  • Carbonell, P., Fichera, D., Pandit, S., Faulon, J.L.: Enumerating metabolic pathways for the production of heterologous target chemicals in chassis organisms. BMC Syst. Biol. 6(1), 10 (2012). https://doi.org/10.1186/1752-0509-6-10

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  • Liu, F., Vilaa, P., Rocha, I., Rocha, M.: Development and application of efficient pathway enumeration algorithms for metabolic engineering applications. Comput. Methods Prog. Biomed. (2014). https://doi.org/10.1016/j.cmpb.2014.11.010

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  • An early discussion about pathway ranking:

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  • Carbonell, P., Planson, A.G., Fichera, D., Faulon, J.L.: A retrosynthetic biology approach to metabolic pathway design for therapeutic production. BMC Syst. Biol. 5(1), 122 (2011). https://doi.org/10.1186/1752-0509-5-122

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  • A proof-of-concept of the application of different approaches to pathway selection and ranking appeared in the report of a recent pressure test for synthetic biology biofoundries:

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Authors and Affiliations

  1. Manchester Institute of Biotechnology, University of Manchester, Manchester, UK

    Pablo Carbonell

Authors
  1. Pablo Carbonell
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Carbonell, P. (2019). Pathway Selection. In: Metabolic Pathway Design. Learning Materials in Biosciences. Springer, Cham. https://doi.org/10.1007/978-3-030-29865-4_7

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