title: Blocking Deprotonation with Retention of Aromaticity in a Plant ent-Copalyl Diphosphate Synthase Leads to Product Rearrangement.
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.
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University, Ames, IA 50011 (USA).
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Potter
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University, Ames, IA 50011 (USA).
authors.forename: Jiachen
authors.initials: J
authors.lastname: Zi
authors.affiliation: Department of Chemistry, University of California, Davis, Davis, CA 95616 (USA).
authors.forename: Young J
authors.initials: YJ
authors.lastname: Hong
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University, Ames, IA 50011 (USA).
authors.forename: Samuel
authors.initials: S
authors.lastname: Schulte
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University, Ames, IA 50011 (USA).
authors.forename: Brandi
authors.initials: B
authors.lastname: Malchow
authors.affiliation: Department of Chemistry, University of California, Davis, Davis, CA 95616 (USA).
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Tantillo
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University, Ames, IA 50011 (USA). rjpeters@iastate.edu.
authors.forename: Reuben J
authors.initials: RJ
authors.lastname: Peters
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D010940:Plant Proteins / Q000737:chemistry*; D010944:Plants / Q000201:enzymology*; D011522:Protons
chemical_list: D010940:Plant Proteins; D011522:Protons; D019883:Alkyl and Aryl Transferases; C090963:ent-kaurene synthetase A
keywords: biosynthesis; cyclizations; natural products; reaction mechanisms; rearrangements