The bHLH transcription factor BIS1 controls the iridoid branch of the monoterpenoid indole alkaloid pathway in Catharanthus roseus

Research output: Contribution to journalArticle


Plants make specialized bioactive metabolites to defend themselves against attackers. The conserved control mechanisms are based on transcriptional activation of the respective plant species-specific biosynthetic pathways by the phytohormone jasmonate. Knowledge of the transcription factors involved, particularly in terpenoid biosynthesis, remains fragmentary. By transcriptome analysis and functional screens in the medicinal plant Catharanthus roseus (Madagascar periwinkle), the unique source of the monoterpenoid indole alkaloid (MIA)-type anticancer drugs vincristine and vinblastine, we identified a jasmonate-regulated basic helix-loop-helix (bHLH) transcription factor from clade IVa inducing the monoterpenoid branch of the MIA pathway. The bHLH iridoid synthesis 1 (BIS1) transcription factor transactivated the expression of all of the genes encoding the enzymes that catalyze the sequential conversion of the ubiquitous terpenoid precursor geranyl diphosphate to the iridoid loganic acid. BIS1 acted in a complementary manner to the previously characterized ethylene response factor Octadecanoid derivative-Responsive Catharanthus APETALA2-domain 3 (ORCA3) that transactivates the expression of several genes encoding the enzymes catalyzing the conversion of loganic acid to the downstream MIAs. In contrast to ORCA3, overexpression of BIS1 was sufficient to boost production of high-value iridoids and MIAs in C. roseus suspension cell cultures. Hence, BIS1 might be a metabolic engineering tool to produce sustainably high-value MIAs in C. roseus plants or cultures.


  • Alex Van Moerkercke
  • Priscille Steensma
  • Fabian Schweizer
  • Jacob Pollier
  • Ivo Gariboldi
  • Richard J. Payne
  • Robin Vanden Bossche
  • Karel Miettinen
  • Javiera Espoz
  • Purin Candra Purnama
  • Franziska Kellner
  • Tuulikki Seppänen-Laakso
  • Sarah E O'Connor
  • Heiko Rischer
  • Johan Memelink
  • Alain Goossens
External organisations
  • John Innes Centre
  • VTT Technical Research Centre of Finland, Helsinki
  • Ghent University
  • Leiden University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biochemistry and Molecular Biology


  • Basic Helix-Loop-Helix Transcription Factors, Catharanthus, Cells, Cultured, Genes, Plant, Indole Alkaloids, Molecular Sequence Data, Transcriptome, Up-Regulation, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)8130-8135
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number26
Publication statusPublished - 2015 Jun 30
Publication categoryResearch
Externally publishedYes