Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis |
| |
| Authors: | Dr. Tsuyoshi Yamamoto Dr. Yuta Tsunematsu Dr. Kodai Hara Dr. Tomohiro Suzuki Dr. Shinji Kishimoto Prof. Dr. Hirokazu Kawagishi Prof. Dr. Hiroshi Noguchi Prof. Dr. Hiroshi Hashimoto Prof. Dr. Yi Tang Prof. Dr. Kinya Hotta Prof. Dr. Kenji Watanabe |
| |
| Affiliation: | 1. Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan;2. Research Institute of Green Science and Technology, Graduate School of Agriculture, Graduate School of Science and Technology, Shizuoka University, Shizuoka, Japan;3. Center for Bioscience Research and Education, Utsunomiya University, Tochigi, Japan;4. Department of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA;5. School of Biosciences, The University of Nottingham Malaysia Campus, Selangor, Malaysia |
| |
| 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 |
|
|
