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Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):E5419-E5428. doi: 10.1073/pnas.1804835115. Epub 2018 May 21.

Short-chain dehydrogenase/reductase governs steroidal specialized metabolites structural diversity and toxicity in the genus Solanum.

Author information

1
Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
2
Structural Proteomics Unit, Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel.
3
Department of Postharvest Science of Fresh Produce, Agricultural Research Organization, Volcani Center, Rishon LeZion 7505101, Israel.
4
Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel; asaph.aharoni@weizmann.ac.il.

Abstract

Thousands of specialized, steroidal metabolites are found in a wide spectrum of plants. These include the steroidal glycoalkaloids (SGAs), produced primarily by most species of the genus Solanum, and metabolites belonging to the steroidal saponins class that are widespread throughout the plant kingdom. SGAs play a protective role in plants and have potent activity in mammals, including antinutritional effects in humans. The presence or absence of the double bond at the C-5,6 position (unsaturated and saturated, respectively) creates vast structural diversity within this metabolite class and determines the degree of SGA toxicity. For many years, the elimination of the double bond from unsaturated SGAs was presumed to occur through a single hydrogenation step. In contrast to this prior assumption, here, we show that the tomato GLYCOALKALOID METABOLISM25 (GAME25), a short-chain dehydrogenase/reductase, catalyzes the first of three prospective reactions required to reduce the C-5,6 double bond in dehydrotomatidine to form tomatidine. The recombinant GAME25 enzyme displayed 3β-hydroxysteroid dehydrogenase/Δ5,4 isomerase activity not only on diverse steroidal alkaloid aglycone substrates but also on steroidal saponin aglycones. Notably, GAME25 down-regulation rerouted the entire tomato SGA repertoire toward the dehydro-SGAs branch rather than forming the typically abundant saturated α-tomatine derivatives. Overexpressing the tomato GAME25 in the tomato plant resulted in significant accumulation of α-tomatine in ripe fruit, while heterologous expression in cultivated eggplant generated saturated SGAs and atypical saturated steroidal saponin glycosides. This study demonstrates how a single scaffold modification of steroidal metabolites in plants results in extensive structural diversity and modulation of product toxicity.

KEYWORDS:

antinutritional; specialized metabolism; steroidal glycoalkaloids; structural diversity; tomato

PMID:
29784829
PMCID:
PMC6003347
DOI:
10.1073/pnas.1804835115
[Indexed for MEDLINE]
Free PMC Article

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