12689-26-8Relevant articles and documents
Enzyme-Catalyzed Inverse-Electron Demand Diels-Alder Reaction in the Biosynthesis of Antifungal Ilicicolin H
Zhang, Zhuan,Jamieson, Cooper S.,Zhao, Yi-Lei,Li, Dehai,Ohashi, Masao,Houk,Tang, Yi
supporting information, p. 5659 - 5663 (2019/04/26)
The pericyclases are a growing superfamily of enzymes that catalyze pericyclic reactions. We report a pericyclase IccD catalyzing an inverse-electron demand Diels-Alder (IEDDA) reaction with a rate acceleration of 3 × 105-fold in the biosynthesis of fungal natural product ilicicolin H. We demonstrate IccD is highly periselective toward the IEDDA cycloaddition over a competing normal electron demand Diels-Alder (NEDDA) reaction from an ambimodal transition state. A predicted flavoenzyme IccE was identified to epimerize the IEDDA product 8-epi-ilicicolin H to ilicicolin H, a step that is critical for the observed antifungal activity of ilicicolin H. Our results reveal the ilicicolin H biosynthetic pathway and add to the collection of pericyclic reactions that are catalyzed by pericyclases.