Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in Catharanthus roseus cells

Heiko Rischer, Matej Oresic, Tuulikki Seppänen-Laakso, Mikko Katajamaa, Freya Lammertyn, Wilson Ardiles-Diaz, Marc C. E. Van Montagu, Dirk Inzé, Kirsi-Marja Oksman-Caldentey, Alain Goossens

Research output: Contribution to journalArticleScientificpeer-review

228 Citations (Scopus)

Abstract

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 (Catharanthus roseus), 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 C. roseus 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.
Original languageEnglish
Pages (from-to)5614-5619
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number14
DOIs
Publication statusPublished - 2006
MoE publication typeA1 Journal article-refereed

Fingerprint

indole alkaloids
Catharanthus roseus
terpenoids
biosynthesis
metabolites
metabolic engineering
genes
medicinal plants
cells
biochemical pathways
vinblastine
vincristine
genome
antineoplastic agents
hormonal regulation
metabolomics
amplified fragment length polymorphism
cell culture
genomics
metabolism

Keywords

  • cell culture
  • periwinkle
  • profiling
  • secondary metabolism
  • jasmonate

Cite this

Rischer, Heiko ; Oresic, Matej ; Seppänen-Laakso, Tuulikki ; Katajamaa, Mikko ; Lammertyn, Freya ; Ardiles-Diaz, Wilson ; Van Montagu, Marc C. E. ; Inzé, Dirk ; Oksman-Caldentey, Kirsi-Marja ; Goossens, Alain. / Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in Catharanthus roseus cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 14. pp. 5614-5619.
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Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in Catharanthus roseus cells. / Rischer, Heiko; Oresic, Matej; Seppänen-Laakso, Tuulikki; Katajamaa, Mikko; Lammertyn, Freya; Ardiles-Diaz, Wilson; Van Montagu, Marc C. E.; Inzé, Dirk; Oksman-Caldentey, Kirsi-Marja; Goossens, Alain.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 14, 2006, p. 5614-5619.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in Catharanthus roseus cells

AU - Rischer, Heiko

AU - Oresic, Matej

AU - Seppänen-Laakso, Tuulikki

AU - Katajamaa, Mikko

AU - Lammertyn, Freya

AU - Ardiles-Diaz, Wilson

AU - Van Montagu, Marc C. E.

AU - Inzé, Dirk

AU - Oksman-Caldentey, Kirsi-Marja

AU - Goossens, Alain

PY - 2006

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N2 - 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 (Catharanthus roseus), 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 C. roseus 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.

AB - 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 (Catharanthus roseus), 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 C. roseus 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.

KW - cell culture

KW - periwinkle

KW - profiling

KW - secondary metabolism

KW - jasmonate

U2 - 10.1073/pnas.0601027103

DO - 10.1073/pnas.0601027103

M3 - Article

VL - 103

SP - 5614

EP - 5619

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 14

ER -