GAME9 regulates the biosynthesis of steroidal alkaloids and upstream isoprenoids in the plant mevalonate pathway

Pablo D. Cárdenas, Prashant D. Sonawane, Jacob Pollier, Robin Vanden Bossche, Veena Dewangan, Efrat Weithorn, Lior Tal, Sagit Meir, Ilana Rogachev, Sergey Malitsky, Ashok P. Giri, Alain Goossens, Saul Burdman and Asaph Aharoni ()
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Pablo D. Cárdenas: Weizmann Institute of Science
Prashant D. Sonawane: Weizmann Institute of Science
Jacob Pollier: Flanders Institute for Biotechnology (VIB)
Robin Vanden Bossche: Flanders Institute for Biotechnology (VIB)
Veena Dewangan: Plant Molecular Biology Unit, Council of Scientific and Industrial Research-National Chemical Laboratory
Efrat Weithorn: Weizmann Institute of Science
Lior Tal: Weizmann Institute of Science
Sagit Meir: Weizmann Institute of Science
Ilana Rogachev: Weizmann Institute of Science
Sergey Malitsky: Weizmann Institute of Science
Ashok P. Giri: Plant Molecular Biology Unit, Council of Scientific and Industrial Research-National Chemical Laboratory
Alain Goossens: Flanders Institute for Biotechnology (VIB)
Saul Burdman: The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem
Asaph Aharoni: Weizmann Institute of Science

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: Abstract Steroidal glycoalkaloids (SGAs) are cholesterol-derived molecules produced by solanaceous species. They contribute to pathogen defence but are toxic to humans and considered as anti-nutritional compounds. Here we show that GLYCOALKALOID METABOLISM 9 (GAME9), an APETALA2/Ethylene Response Factor, related to regulators of alkaloid production in tobacco and Catharanthus roseus, controls SGA biosynthesis. GAME9 knockdown and overexpression in tomato and potato alters expression of SGAs and upstream mevalonate pathway genes including the cholesterol biosynthesis gene STEROL SIDE CHAIN REDUCTASE 2 (SSR2). Levels of SGAs, C24-alkylsterols and the upstream mevalonate and cholesterol pathways intermediates are modified in these plants. Δ(7)-STEROL-C5(6)-DESATURASE (C5-SD) in the hitherto unresolved cholesterol pathway is a direct target of GAME9. Transactivation and promoter-binding assays show that GAME9 exerts its activity either directly or cooperatively with the SlMYC2 transcription factor as in the case of the C5-SD gene promoter. Our findings provide insight into the regulation of SGA biosynthesis and means for manipulating these metabolites in crops.

Date: 2016
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DOI: 10.1038/ncomms10654

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