Blocking Deprotonation with Retention of Aromaticity in a Plant ent‐Copalyl Diphosphate Synthase Leads to Product Rearrangement. Issue 2 (25th November 2015)

• Record Type: Journal Article
• Authors: Potter, Kevin C.; Zi, Jiachen; Hong, Young J.; Schulte, Samuel; Malchow, Brandi; Tantillo, Dean J.; Peters, Reuben J.
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 2(2016)
• Page Start: 634
• Page End: 638
• Publication Date: 2015-11-25
• Subjects: biosynthesis -- cyclizations -- natural products -- reaction mechanisms -- rearrangements; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201509060
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Substitution of a histidine, comprising part of the catalytic base group in the ent‐copalyl diphosphate synthases found in all seed plants for gibberellin phytohormone metabolism, by a larger aromatic residue leads to rearrangements. Through a series of 1, 2‐hydride and methyl shifts of the initially formed bicycle predominant formation of (−)‐kolavenyl diphosphate is observed. Further mutational analysis and quantum chemical calculations provide mechanistic insight into the basis for this profound effect on product outcome. Abstract : Make the swap : Substitution of histidine, comprising part of the catalytic base group in the ent ‐copalyl diphosphate synthases, leads to rearrangements. Through a series of 1, 2‐hydride and methyl shifts of the initially formed bicycle, predominant formation of (−)‐kolavenyl diphosphate is observed. Further mutational analysis and quantum chemical calculations provide mechanistic insight into the basis for this profound effect on product outcome.