Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis.
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.
['Yamamoto|Tsuyoshi|T|', 'Tsunematsu|Yuta|Y|', 'Hara|Kodai|K|', 'Suzuki|Tomohiro|T|', 'Kishimoto|Shinji|S|', 'Kawagishi|Hirokazu|H|', 'Noguchi|Hiroshi|H|', 'Hashimoto|Hiroshi|H|', 'Tang|Yi|Y|', 'Hotta|Kinya|K|', 'Watanabe|Kenji|K|']
isomerization polyketides biosynthesis natural products enzymes