Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis. Issue 21 (13th April 2016)

• Record Type: Journal Article
• Authors: Yamamoto, Tsuyoshi; Tsunematsu, Yuta; Hara, Kodai; Suzuki, Tomohiro; Kishimoto, Shinji; Kawagishi, Hirokazu; Noguchi, Hiroshi; Hashimoto, Hiroshi; Tang, Yi; Hotta, Kinya; Watanabe, Kenji
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 21(2016)
• Page Start: 6207
• Page End: 6210
• Publication Date: 2016-04-13
• Subjects: biosynthesis -- enzymes -- isomerization -- natural products -- polyketides; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201600940
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : Strike a 'PsoE' : An in vitro study revealed that the glutathione S‐transferase PsoE required the bifunctional PsoF to complete the isomerization of a pseurotin biosynthetic pathway intermediate. The PsoE crystal structure indicated that the intermediate–glutathione conjugation to be the sole function of PsoE. PsoF was identified to have an additional oxidative isomerase activity, thus making it a trifunctional enzyme which is key to generating complexity in pseurotin biosynthesis.