Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis. (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. Volume 128:Number 21(2016)
• Page Start: 6315
• Page End: 6318
• Publication Date: 2016-04-13
• Subjects: Biosynthese -- Enzyme -- Isomerisierungen -- Naturstoffe -- Polyketide; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201600940
• Languages: English
• ISSNs: 0044-8249

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.