title: Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis.
abstract: Geometric isomerization can expand the scope of biological activities of natural products. The observed chemical diversity among the pseurotin-type fungal secondary metabolites is in part generated by a trans to cis isomerization of an olefin. In vitro characterizations of pseurotin biosynthetic enzymes revealed that the glutathione S-transferase PsoE requires participation of the bifunctional C-methyltransferase/epoxidase PsoF to complete the trans to cis isomerization of the pathway intermediate presynerazol. The crystal structure of the PsoE/glutathione/presynerazol complex indicated stereospecific glutathione-presynerazol conjugate formation is the principal function of PsoE. Moreover, PsoF was identified to have an additional, unexpected oxidative isomerase activity, thus making it a trifunctional enzyme which is key to the complexity generation in pseurotin biosynthesis. Through the study, we identified a novel mechanism of accomplishing a seemingly simple trans to cis isomerization reaction.
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tsunematsu
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
authors.forename: Kodai
authors.initials: K
authors.lastname: Hara
authors.affiliation: Research Institute of Green Science and Technology, Graduate School of Agriculture, Graduate School of Science and Technology, Shizuoka University, Shizuoka, 422-8529, Japan.|Center for Bioscience Research and Education, Utsunomiya University, Tochigi, 321-8505, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kishimoto
authors.affiliation: Research Institute of Green Science and Technology, Graduate School of Agriculture, Graduate School of Science and Technology, Shizuoka University, Shizuoka, 422-8529, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kawagishi
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Noguchi
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Department of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.affiliation: School of Biosciences, The University of Nottingham Malaysia Campus, Selangor, 43500, Malaysia.
authors.forename: Kinya
authors.initials: K
authors.lastname: Hotta
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan. kenji55@u-shizuoka-ken.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
keywords: biosynthesis; enzymes; isomerization; natural products; polyketides