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Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis

Yamamoto T 1 , Tsunematsu Y 1 , Hara K 1 , Suzuki T 2 , Kishimoto S 1 , Kawagishi H 2 Show all authors , Noguchi H 1 , Hashimoto H 1 , Tang Y 3 , Hotta K 4 , Watanabe K 5

Affiliations 

  • 1 Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan
  • 2 Research Institute of Green Science and Technology, Graduate School of Agriculture, Graduate School of Science and Technology, Shizuoka University, Shizuoka, 422-8529, Japan
  • 3 Department of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, USA
  • 4 School of Biosciences, The University of Nottingham Malaysia Campus, Selangor, 43500, Malaysia
  • 5 Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan. kenji55@u-shizuoka-ken.ac.jp
Angew Chem Int Ed Engl, 2016 05 17;55(21):6207-10.
PMID: 27072782 DOI: 10.1002/anie.201600940

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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