Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis

Tsuyoshi Yamamoto; Yuta Tsunematsu; Kodai Hara; Tomohiro Suzuki; Shinji Kishimoto; Hirokazu Kawagishi; Hiroshi Noguchi; Hiroshi Hashimoto; Yi Tang; Kinya Hotta; Kenji Watanabe

doi:10.1002/anie.201600940

Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis

Angew Chem Int Ed Engl. 2016 May 17;55(21):6207-10. doi: 10.1002/anie.201600940. Epub 2016 Apr 13.

Authors

Affiliations

¹ Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
² Research Institute of Green Science and Technology, Graduate School of Agriculture, Graduate School of Science and Technology, Shizuoka University, Shizuoka, 422-8529, Japan.
³ Center for Bioscience Research and Education, Utsunomiya University, Tochigi, 321-8505, Japan.
⁴ Department of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, USA.
⁵ School of Biosciences, The University of Nottingham Malaysia Campus, Selangor, 43500, Malaysia.
⁶ Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan. kenji55@u-shizuoka-ken.ac.jp.

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.

Keywords: biosynthesis; enzymes; isomerization; natural products; polyketides.

Publication types

Research Support, Non-U.S. Gov't

Abstract

Publication types

Grants and funding