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

Alex Van Moerkercke, Priscille Steensma, Fabian Schweizer, Jacob Pollier, Ivo Gariboldi, Richard 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

Research output: Contribution to journalArticleScientificpeer-review

68 Citations (Scopus)

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 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.
Original languageEnglish
Pages (from-to)8130-8135
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number26
DOIs
Publication statusPublished - 2015
MoE publication typeA1 Journal article-refereed

Fingerprint

basic helix-loop-helix transcription factors
indole alkaloids
Catharanthus roseus
monoterpenoids
Catharanthus
synthesis
terpenoids
transcription factors
chemical derivatives
vinblastine
iridoids
vincristine
metabolic engineering
antineoplastic agents
acids
transcriptional activation
enzymes
transcriptomics
plant hormones
cell suspension culture

Keywords

  • basic helix loop helix
  • Catharanthus roseus
  • jasmonate
  • Madagascar periwinkle
  • iridoids

Cite this

Van Moerkercke, Alex ; Steensma, Priscille ; Schweizer, Fabian ; Pollier, Jacob ; Gariboldi, Ivo ; Payne, Richard ; Vanden Bossche, Robin ; Miettinen, Karel ; Espoz, Javiera ; Purnama, Purin Candra ; Kellner, Franziska ; Seppänen-Laakso, Tuulikki ; O'Connor, Sarah E. ; Rischer, Heiko ; Memelink, Johan ; Goossens, Alain. / The bHLH transcription factor BIS1 controls the iridoid branch of the monoterpenoid indole alkaloid pathway in Catharanthus roseus. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 26. pp. 8130-8135.
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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 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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author = "{Van Moerkercke}, Alex and Priscille Steensma and Fabian Schweizer and Jacob Pollier and Ivo Gariboldi and Richard Payne and {Vanden Bossche}, Robin and Karel Miettinen and Javiera Espoz and Purnama, {Purin Candra} and Franziska Kellner and Tuulikki Sepp{\"a}nen-Laakso and O'Connor, {Sarah E.} and Heiko Rischer and Johan Memelink and Alain Goossens",
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Van Moerkercke, A, Steensma, P, Schweizer, F, Pollier, J, Gariboldi, I, Payne, R, Vanden Bossche, R, Miettinen, K, Espoz, J, Purnama, PC, Kellner, F, Seppänen-Laakso, T, O'Connor, SE, Rischer, H, Memelink, J & Goossens, A 2015, 'The bHLH transcription factor BIS1 controls the iridoid branch of the monoterpenoid indole alkaloid pathway in Catharanthus roseus', Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 26, pp. 8130-8135. https://doi.org/10.1073/pnas.1504951112

The bHLH transcription factor BIS1 controls the iridoid branch of the monoterpenoid indole alkaloid pathway in Catharanthus roseus. / Van Moerkercke, Alex; Steensma, Priscille; Schweizer, Fabian; Pollier, Jacob; Gariboldi, Ivo; Payne, Richard; Vanden Bossche, Robin; Miettinen, Karel; Espoz, Javiera; Purnama, Purin Candra; Kellner, Franziska; Seppänen-Laakso, Tuulikki; O'Connor, Sarah E.; Rischer, Heiko; Memelink, Johan; Goossens, Alain.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 26, 2015, p. 8130-8135.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - The bHLH transcription factor BIS1 controls the iridoid branch of the monoterpenoid indole alkaloid pathway in Catharanthus roseus

AU - Van Moerkercke, Alex

AU - Steensma, Priscille

AU - Schweizer, Fabian

AU - Pollier, Jacob

AU - Gariboldi, Ivo

AU - Payne, Richard

AU - Vanden Bossche, Robin

AU - Miettinen, Karel

AU - Espoz, Javiera

AU - Purnama, Purin Candra

AU - Kellner, Franziska

AU - Seppänen-Laakso, Tuulikki

AU - O'Connor, Sarah E.

AU - Rischer, Heiko

AU - Memelink, Johan

AU - Goossens, Alain

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - basic helix loop helix

KW - Catharanthus roseus

KW - jasmonate

KW - Madagascar periwinkle

KW - iridoids

U2 - 10.1073/pnas.1504951112

DO - 10.1073/pnas.1504951112

M3 - Article

VL - 112

SP - 8130

EP - 8135

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 - 26

ER -