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Enzyme-Catalyzed Inverse-Electron Demand Diels-Alder Reaction in the Biosynthesis of Antifungal Ilicicolin H.

Zhuan ZhangCooper S JamiesonYi-Lei ZhaoDe-Hai LiMasao OhashiKendall N HoukYi Tang
Published in: Journal of the American Chemical Society (2019)
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.
Keyphrases
  • electron transfer
  • cell wall
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  • solar cells
  • electron microscopy
  • genome wide
  • gene expression
  • dna methylation
  • transcription factor