Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis
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- 作者：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 and Prof. Dr. Kenji Watanabe
- 刊名：Angewandte Chemie
- 出版年：2016
- 出版时间：May 17, 2016
- 年：2016
- 卷：128
- 期：21
- 页码：6315-6318
- 全文大小：1621K
- ISSN：1521-3757
文摘
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.