The bHLH transcription factor BIS1 controls the iridoid branch of the monoterpenoid indole alkaloid pathway in Catharanthus roseus
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:112 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 112(2015), 26 vom: 30. Juni, Seite 8130-5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Van Moerkercke, Alex [VerfasserIn] |
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| Links: |
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| Themen: |
Basic Helix-Loop-Helix Transcription Factors |
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| Anmerkungen: |
Date Completed 17.11.2015 Date Revised 16.07.2022 published: Print-Electronic BioProject: PRJNA276552 GENBANK: KM409646, KP963953, KP963954, KP963955, KP963956, KP963957, KP963958, KP963959 Citation Status MEDLINE |
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| doi: |
10.1073/pnas.1504951112 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM250016648 |
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| 245 | 1 | 4 | |a The bHLH transcription factor BIS1 controls the iridoid branch of the monoterpenoid indole alkaloid pathway in Catharanthus roseus |
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| 500 | |a published: Print-Electronic | ||
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| 500 | |a GENBANK: KM409646, KP963953, KP963954, KP963955, KP963956, KP963957, KP963958, KP963959 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Catharanthus roseus | |
| 650 | 4 | |a Madagascar periwinkle | |
| 650 | 4 | |a basic helix loop helix | |
| 650 | 4 | |a iridoids | |
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| 650 | 7 | |a Basic Helix-Loop-Helix Transcription Factors |2 NLM | |
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| 700 | 1 | |a Steensma, Priscille |e verfasserin |4 aut | |
| 700 | 1 | |a Schweizer, Fabian |e verfasserin |4 aut | |
| 700 | 1 | |a Pollier, Jacob |e verfasserin |4 aut | |
| 700 | 1 | |a Gariboldi, Ivo |e verfasserin |4 aut | |
| 700 | 1 | |a Payne, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Vanden Bossche, Robin |e verfasserin |4 aut | |
| 700 | 1 | |a Miettinen, Karel |e verfasserin |4 aut | |
| 700 | 1 | |a Espoz, Javiera |e verfasserin |4 aut | |
| 700 | 1 | |a Purnama, Purin Candra |e verfasserin |4 aut | |
| 700 | 1 | |a Kellner, Franziska |e verfasserin |4 aut | |
| 700 | 1 | |a Seppänen-Laakso, Tuulikki |e verfasserin |4 aut | |
| 700 | 1 | |a O'Connor, Sarah E |e verfasserin |4 aut | |
| 700 | 1 | |a Rischer, Heiko |e verfasserin |4 aut | |
| 700 | 1 | |a Memelink, Johan |e verfasserin |4 aut | |
| 700 | 1 | |a Goossens, Alain |e verfasserin |4 aut | |
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