Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in <i>Catharanthus roseus</i> cells

  • Heiko Rischer
    *VTT Technical Research Centre of Finland, Tietotie 2, FIN-02044 VTT, Espoo, Finland;
  • Matej Orešič
    *VTT Technical Research Centre of Finland, Tietotie 2, FIN-02044 VTT, Espoo, Finland;
  • Tuulikki Seppänen-Laakso
    *VTT Technical Research Centre of Finland, Tietotie 2, FIN-02044 VTT, Espoo, Finland;
  • Mikko Katajamaa
    Turku Centre for Biotechnology, Tykistökatu 6, FIN-20521, Turku, Finland; and
  • Freya Lammertyn
    Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology, Ghent University, B-9052 Ghent, Belgium
  • Wilson Ardiles-Diaz
    Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology, Ghent University, B-9052 Ghent, Belgium
  • Marc C. E. Van Montagu
    Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology, Ghent University, B-9052 Ghent, Belgium
  • Dirk Inzé
    Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology, Ghent University, B-9052 Ghent, Belgium
  • Kirsi-Marja Oksman-Caldentey
    *VTT Technical Research Centre of Finland, Tietotie 2, FIN-02044 VTT, Espoo, Finland;
  • Alain Goossens
    Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology, Ghent University, B-9052 Ghent, Belgium

抄録

<jats:p> Rational engineering of complicated metabolic networks involved in the production of biologically active plant compounds has been greatly impeded by our poor understanding of the regulatory and metabolic pathways underlying the biosynthesis of these compounds. Whereas comprehensive genome-wide functional genomics approaches can be successfully applied to analyze a select number of model plants, these holistic approaches are not yet available for the study of nonmodel plants that include most, if not all, medicinal plants. We report here a comprehensive profiling analysis of the Madagascar periwinkle ( <jats:italic>Catharanthus roseus</jats:italic> ), a source of the anticancer drugs vinblastine and vincristine. Genome-wide transcript profiling by cDNA-amplified fragment-length polymorphism combined with metabolic profiling of elicited <jats:italic>C. roseus</jats:italic> cell cultures yielded a collection of known and previously undescribed transcript tags and metabolites associated with terpenoid indole alkaloids. Previously undescribed gene-to-gene and gene-to-metabolite networks were drawn up by searching for correlations between the expression profiles of 417 gene tags and the accumulation profiles of 178 metabolite peaks. These networks revealed that the different branches of terpenoid indole alkaloid biosynthesis and various other metabolic pathways are subject to differing hormonal regulation. These networks also served to identify a select number of genes and metabolites likely to be involved in the biosynthesis of terpenoid indole alkaloids. This study provides the basis for a better understanding of periwinkle secondary metabolism and increases the practical potential of metabolic engineering of this important medicinal plant. </jats:p>

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