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Third DWF1 paralog in Solanaceae, sterol Δ24-isomerase, branches withanolide biosynthesis from the general phytosterol pathway.
Knoch, Eva; Sugawara, Satoko; Mori, Tetsuya; Poulsen, Christian; Fukushima, Atsushi; Harholt, Jesper; Fujimoto, Yoshinori; Umemoto, Naoyuki; Saito, Kazuki.
Afiliação
  • Knoch E; RIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan.
  • Sugawara S; RIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan.
  • Mori T; RIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan.
  • Poulsen C; Carlsberg Research Laboratory, 1778 Copenhagen, Denmark.
  • Fukushima A; RIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan.
  • Harholt J; Carlsberg Research Laboratory, 1778 Copenhagen, Denmark.
  • Fujimoto Y; Department of Chemistry, Tokyo Institute of Technology, Meguro, Tokyo 152-8550, Japan.
  • Umemoto N; RIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan.
  • Saito K; RIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan; kazuki.saito@riken.jp.
Proc Natl Acad Sci U S A ; 115(34): E8096-E8103, 2018 08 21.
Article em En | MEDLINE | ID: mdl-30082386
A large part of chemodiversity of plant triterpenes is due to the modification of their side chains. Reduction or isomerization of double bonds in the side chains is often an important step for the diversification of triterpenes, although the enzymes involved are not fully understood. Withanolides are a large group of structurally diverse C28 steroidal lactones derived from 24-methylenecholesterol. These compounds are found in the Indian medicinal plant Withania somnifera, also known as ashwagandha, and other members of the Solanaceae. The pathway for withanolide biosynthesis is unknown, preventing sustainable production via white biotechnology and downstream pharmaceutical usages. In the present study, based on genome and transcriptome data we have identified a key enzyme in the biosynthesis of withanolides: a DWF1 paralog encoding a sterol Δ24-isomerase (24ISO). 24ISO originated from DWF1 after two subsequent duplication events in Solanoideae plants. Withanolides and 24ISO appear only in the medicinal plants in the Solanoideae, not in crop plants such as potato and tomato, indicating negative selection during domestication. 24ISO is a unique isomerase enzyme evolved from a reductase and as such has maintained the FAD-binding oxidoreductase structure and requirement for NADPH. Using phylogenetic, metabolomic, and gene expression analysis in combination with heterologous expression and virus-induced gene silencing, we showed that 24ISO catalyzes the conversion of 24-methylenecholesterol to 24-methyldesmosterol. We propose that this catalytic step is the committing step in withanolide biosynthesis, opening up elucidation of the whole pathway and future larger-scale sustainable production of withanolides and related compounds with pharmacological properties.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Filogenia / Proteínas de Plantas / Esteroide Isomerases / Regulação Enzimológica da Expressão Gênica / Regulação da Expressão Gênica de Plantas / Withania / Vitanolídeos Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Japão País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Filogenia / Proteínas de Plantas / Esteroide Isomerases / Regulação Enzimológica da Expressão Gênica / Regulação da Expressão Gênica de Plantas / Withania / Vitanolídeos Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Japão País de publicação: Estados Unidos