Extended Metabolic Space Modeling

  • Pablo CarbonellEmail author
  • Baudoin Delépine
  • Jean-Loup Faulon
Part of the Methods in Molecular Biology book series (MIMB, volume 1671)


Determining the fraction of the chemical space that can be processed in vivo by using natural and synthetic biology devices is crucial for the development of advanced synthetic biology applications. The extended metabolic space is a coding system based on molecular signatures that enables the derivation of reaction rules for metabolic reactions and the enumeration of all possible substrates and products corresponding to the rules. The extended metabolic space expands capabilities for controlling the production, processing, sensing, and the release of specific molecules in chassis organisms.

Key words

Metabolic modeling Enzyme reactions Pathways Products Chassis 



The authors acknowledge funding from the BBSRC under grant BB/M017702/1, “Centre for synthetic biology of fine and speciality chemicals.” J.L.F. acknowledges funding provided by the ANR under grant ANR-15-CE21-008. B.D. is affiliated to the Doctoral School Structure et Dynamique des Systèmes Vivant, Université Paris-Saclay.


  1. 1.
    Wishart DS, Jewison T, Guo AC et al (2013) HMDB 3.0—the human metabolome database in 2013. Nucleic Acids Res 41:D801–D807. doi: 10.1093/nar/gks1065 CrossRefPubMedGoogle Scholar
  2. 2.
    Schellenberger J, Park J, Conrad T, Palsson B (2010) BiGG: a biochemical genetic and genomic knowledgebase of large scale metabolic reconstructions. BMC Bioinformatics 11:213. doi: 10.1186/1471-2105-11-213 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Tu BP, Mohler RE, Liu JC et al (2007) Cyclic changes in metabolic state during the life of a yeast cell. Proc Natl Acad Sci U S A 104:16886–16891. doi: 10.1073/pnas.0708365104 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Carbonell P, Carlsson L, Faulon J-L (2013) Stereo signature molecular descriptor. J Chem Inf Model 53:887–897. doi: 10.1021/ci300584r CrossRefPubMedGoogle Scholar
  5. 5.
    Carbonell P, Faulon J-L (2010) Molecular signatures-based prediction of enzyme promiscuity. Bioinformatics 26:2012–2019. doi: 10.1093/bioinformatics/btq317 CrossRefPubMedGoogle Scholar
  6. 6.
    Dougherty MJ, Arnold FH (2009) Directed evolution: new parts and optimized function. Curr Opin Biotechnol 20:486–491. doi: 10.1016/j.copbio.2009.08.005 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Kim J, Kershner JP, Novikov Y et al (2010) Three serendipitous pathways in E. coli can bypass a block in pyridoxal-5-phosphate synthesis. Mol Syst Biol. doi: 10.1038/msb.2010.88
  8. 8.
    Moretti S, Martin O, Van Du Tran T et al (2016) MetaNetX/MNXref reconciliation of metabolites and biochemical reactions to bring together genome-scale metabolic networks. Nucleic Acids Res 44:D523–D526. doi: 10.1093/nar/gkv1117 CrossRefPubMedGoogle Scholar
  9. 9.
    Chelliah V, Juty N, Ajmera I et al (2014) BioModels: ten-year anniversary. Nucleic Acids Res 43:D542–D548. doi: 10.1093/nar/gku1181 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Terzer M, Stelling J (2008) Large-scale computation of elementary flux modes with bit pattern trees. Bioinformatics 24:2229–2235. doi: 10.1093/bioinformatics/btn401 CrossRefPubMedGoogle Scholar
  11. 11.
    Shannon P, Markiel A, Ozier O et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504. doi: 10.1101/gr.1239303 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Berthold MR, Cebron N, Dill F et al (2009) KNIME – the Konstanz information miner. SIGKDD Explor 11:26–31. doi: 10.1145/1656274.1656280 CrossRefGoogle Scholar
  13. 13.
    Ebrahim A, Lerman JAJ, Palsson BO, Hyduke DR (2013) COBRApy: COnstraints-Based Reconstruction and Analysis for python. BMC Syst Biol 7:74. doi: 10.1186/1752-0509-7-74 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Kanehisa M, Goto S, Sato Y et al (2012) KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res 40:D109–D114. doi: 10.1093/nar/gkr988 CrossRefPubMedGoogle Scholar
  15. 15.
    Caspi R, Altman T, Dreher K et al (2012) The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res 40:D742–D753. doi: 10.1093/nar/gkr1014 CrossRefPubMedGoogle Scholar
  16. 16.
    Chang A, Schomburg I, Placzek S et al (2014) BRENDA in 2015: exciting developments in its 25th year of existence. Nucleic Acids Res. doi: 10.1093/nar/gku1068
  17. 17.
    Hucka M, Finney A, Sauro HM et al (2003) The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19:524–531CrossRefPubMedGoogle Scholar
  18. 18.
    Carbonell P, Fichera D, Pandit S, Faulon JL (2012) Enumerating metabolic pathways for the production of heterologous target chemicals in chassis organisms. BMC Syst Biol 6:10. doi: 10.1186/1752-0509-6-10 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Zanghellini J, Ruckerbauer DE, Hanscho M, Jungreuthmayer C (2013) Elementary flux modes in a nutshell: properties, calculation and applications. Biotechnol J 8:1009–1016. doi: 10.1002/biot.201200269 CrossRefPubMedGoogle Scholar
  20. 20.
    Carbonell P, Planson A-GG, Faulon J-LL (2013) Retrosynthetic design of heterologous pathways. Methods Mol Biol 985:149–173. doi: 10.1007/978-1-62703-299-5_9 CrossRefPubMedGoogle Scholar
  21. 21.
    Carbonell P, Parutto P, Herisson J et al (2014) XTMS: pathway design in an eXTended metabolic space. Nucleic Acids Res:W389–W394. doi: 10.1093/nar/gku362
  22. 22.
    Carbonell P, Parutto P, Baudier C et al (2014) Retropath: automated pipeline for embedded metabolic circuits. ACS Synth Biol 3:565–577. doi: 10.1021/sb4001273 CrossRefPubMedGoogle Scholar
  23. 23.
    Delpine B, Libis V, Carbonell P, Faulon J-L (2016) SensiPath: computer-aided design of sensing-enabling metabolic pathways. Nucleic Acids Res. doi: 10.1093/nar/gkw305
  24. 24.
    O’Boyle NM, Banck M, James CA et al (2011) Open babel: an open chemical toolbox. J Cheminform 3:33. doi: 10.1186/1758-2946-3-33 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  • Pablo Carbonell
    • 1
    Email author
  • Baudoin Delépine
    • 2
    • 3
  • Jean-Loup Faulon
    • 1
    • 2
    • 3
  1. 1.Manchester Centre for Fine and Speciality Chemicals (SYNBIOCHEM), Manchester Institute of BiotechnologyUniversity of ManchesterManchesterUK
  2. 2.iSSB, Genopole, CNRS, UEVEUniversité Paris-SaclayÉvryFrance
  3. 3.MICALIS Institute, INRAJouy-en-Josas CedexFrance

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