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Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis
Author(s) -
Yamamoto Tsuyoshi,
Tsunematsu Yuta,
Hara Kodai,
Suzuki Tomohiro,
Kishimoto Shinji,
Kawagishi Hirokazu,
Noguchi Hiroshi,
Hashimoto Hiroshi,
Tang Yi,
Hotta Kinya,
Watanabe Kenji
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201600940
Subject(s) - isomerization , chemistry , isomerase , stereospecificity , biosynthesis , stereochemistry , glutathione , enzyme , biochemistry , catalysis
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.