Preprint / Version 1

Third DWF1 paralog in Solanaceae, sterol Δ24-isomerase, branches withanolide biosynthesis from the general phytosterol pathway

Authors

  • Eva Knoch aRIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan;
  • Satoko Sugawara aRIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan;
  • Tetsuya Mori aRIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan;
  • Christian Poulsen bCarlsberg Research Laboratory, 1778 Copenhagen, Denmark;
  • Atsushi Fukushima aRIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan;
  • Jesper Harholt bCarlsberg Research Laboratory, 1778 Copenhagen, Denmark;
  • Yoshinori Fujimoto cDepartment of Chemistry, Tokyo Institute of Technology, Meguro, Tokyo 152-8550, Japan;
  • Naoyuki Umemoto aRIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan;
  • Kazuki Saito aRIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan;

Keywords:

sterol biosynthesis, Withania somnifera, sterol 24-isomerase, withanolides, pathway evolution

Abstract

Significance Withanolides form a major class of plant steroids with unique side-chain modifications. Withanolides are one of the main active components in an Indian Ayurvedic medicinal plant, ashwagandha, which has been used for over 3,000 y. Because of their highly diversified structures, withanolides are promising pharmacological compounds with proven antiinflammatory and anticancer properties. We identified a sterol Δ24-isomerase (24ISO) catalyzing the first committed step in the biosynthesis of withanolides and related compounds. Identification of 24ISO paves the way for targeted manipulations to increase withanolide yields and as a starting point to elucidate the downstream pathway of yet-unknown withanolide biosynthesis. This study also demonstrates how the evolution of enzymes catalyzing double-bond modifications of triterpene side chains lead to diversity in structures and functions. Keywords: sterol biosynthesis, Withania somnifera, sterol 24-isomerase, withanolides, pathway evolution

Author Biography

Kazuki Saito, aRIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan;

dGraduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan

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