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In Silico Biology 5, 0012 (2004); ©2004, Bioinformation Systems e.V.  

Metabolites and pathway flexibility

Thomas Dandekar1,2,* and Steffen Schmidt3

1 Dept. of Bioinformatics, Biocenter, Am Hubland, D-97074 Würzburg, Germany,
2 European Molecular Biology Laboratory, Postfach 102209, D-69012 Heidelberg, Germany
3 Brigham and Women's Hospital, Division of Genetics, New Research Building; 77 Ave Louis Pasteur; Boston, MA 02115, USA; Email:

* Corresponding author; Phone: +49-931-888 4551; Fax: +49-931-888 4552; Email:

Edited by E. Wingender; received September 30, 2004; revised and accepted October 27, 2004; published November 09, 2004


Flexibility of metabolites and enzymes is investigated (i) on the level of the individual molecule, (ii) on the pathway level and (iii) combined effects on the systems and network level. Tools and results from our current research are summarized including data from our metabolite enzyme database. Including our latest census we find frequently used metabolites stimulate evolutionary flexibility in specific enzyme superfamilies. Furthermore, simultaneous changes of reactions and metabolites are observed in these flexible enzyme superfamilies. Both effects provide a strong source for resistance in parasites and pathogens. Specific adaptations scenarios and some counter strategies are discussed.

Key words: flexibility, metabolites, enzyme family, resistance, adaptation, pathway, network