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

Van Moerkercke, Alex LU ; Steensma, Priscille; Schweizer, Fabian; Pollier, Jacob; Gariboldi, Ivo; Payne, Richard J.; Vanden Bossche, Robin; Miettinen, Karel; Espoz, Javiera and Purnama, Purin Candra, et al. (2015) In Proceedings of the National Academy of Sciences of the United States of America 112(26). p.8130-8135
Abstract

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... (More)

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.

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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
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Proceedings of the National Academy of Sciences of the United States of America
volume
112
issue
26
pages
6 pages
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National Acad Sciences
external identifiers
  • scopus:84937947390
ISSN
1091-6490
DOI
10.1073/pnas.1504951112
language
English
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no
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244a6357-37d4-4bfa-b13c-ff5f9d9f5da4
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2017-11-06 11:30:09
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2018-01-07 12:24:53
@article{244a6357-37d4-4bfa-b13c-ff5f9d9f5da4,
  abstract     = {<p>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.</p>},
  author       = {Van Moerkercke, Alex and Steensma, Priscille and Schweizer, Fabian and Pollier, Jacob and Gariboldi, Ivo and Payne, Richard J. and Vanden Bossche, Robin and Miettinen, Karel and Espoz, Javiera and Purnama, Purin Candra and Kellner, Franziska and Seppänen-Laakso, Tuulikki and O'Connor, Sarah E and Rischer, Heiko and Memelink, Johan and Goossens, Alain},
  issn         = {1091-6490},
  keyword      = {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},
  language     = {eng},
  month        = {06},
  number       = {26},
  pages        = {8130--8135},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences of the United States of America},
  title        = {The bHLH transcription factor BIS1 controls the iridoid branch of the monoterpenoid indole alkaloid pathway in Catharanthus roseus},
  url          = {http://dx.doi.org/10.1073/pnas.1504951112},
  volume       = {112},
  year         = {2015},
}