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Pathway Selection

  • Pablo Carbonell
Chapter
Part of the Learning Materials in Biosciences book series (LMB)

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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Further Reading

  1. Hypergraph techniques for metabolic pathway enumeration:Google Scholar
  2. 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 CrossRefGoogle Scholar
  3. 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 Google Scholar
  4. An early discussion about pathway ranking:Google Scholar
  5. 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 CrossRefGoogle Scholar
  6. 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:Google Scholar
  7. Casini, A., Chang, F.Y., Eluere, R., King, A.M., Young, E.M., Dudley, Q.M., Karim, A., Pratt, K., Bristol, C., Forget, A., Ghodasara, A., Warden-Rothman, R., Gan, R., Cristofaro, A., Borujeni, A.E., Ryu, M.H., Li, J., Kwon, Y.C., Wang, H., Tatsis, E., Rodriguez-Lopez, C., O’Connor, S., Medema, M.H., Fischbach, M.A., Jewett, M.C., Voigt, C., Gordon, D.B.: A pressure test to make 10 molecules in 90 days: external evaluation of methods to engineer biology. J. Am. Chem. Soc. 140(12), 4302–4316 (2018).  https://doi.org/10.1021/jacs.7b13292 CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Pablo Carbonell
    • 1
  1. 1.Manchester Institute of BiotechnologyUniversity of ManchesterManchesterUK

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