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

被引:157
作者
Van Moerkercke, Alex [1 ,2 ]
Steensma, Priscille [3 ]
Schweizer, Fabian [1 ,2 ]
Pollier, Jacob [1 ,2 ]
Gariboldi, Ivo [3 ]
Payne, Richard [4 ]
Bossche, Robin Vanden [1 ,2 ]
Miettinen, Karel [1 ,2 ]
Espoz, Javiera [3 ]
Purnama, Purin Candra [3 ]
Kellner, Franziska [4 ]
Seppanen-Laakso, Tuulikki [5 ]
O'Connor, Sarah E. [4 ]
Rischer, Heiko [5 ]
Memelink, Johan [3 ]
Goossens, Alain [1 ,2 ]
机构
[1] Flanders Inst Biotechnol VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium
[2] Univ Ghent, Dept Plant Biotechnol & Bioinformat, B-9052 Ghent, Belgium
[3] Leiden Univ, Inst Biol, NL-2300 RA Leiden, Netherlands
[4] John Innes Ctr, Dept Biol Chem, Norwich NR4 7UH, Norfolk, England
[5] VTT Tech Res Ctr Finland Ltd, FIN-02044 Espoo, Finland
基金
英国生物技术与生命科学研究理事会;
关键词
basic helix loop helix; Catharanthus roseus; jasmonate; Madagascar periwinkle; iridoids; SYNTHASE GENE-EXPRESSION; MADAGASCAR PERIWINKLE; SECONDARY METABOLISM; BIOSYNTHESIS; PLANT; MYC2; STRICTOSIDINE; REPRESSORS; PROTEINS; ORCA3;
D O I
10.1073/pnas.1504951112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:8130 / 8135
页数:6
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