title: A single residue change leads to a hydroxylated product from the class II diterpene cyclization catalyzed by abietadiene synthase.
abstract: Class II diterpene cyclases catalyze bicyclization of geranylgeranyl diphosphate. While this reaction typically is terminated via methyl deprotonation to yield copalyl diphosphate, in rare cases hydroxylated bicycles are produced instead. Abietadiene synthase is a bifunctional diterpene cyclase that usually produces a copalyl diphosphate intermediate. Here it is shown that substitution of aspartate for a conserved histidine in the class II active site of abietadiene synthase leads to selective production of 8α-hydroxy-CPP instead, demonstrating striking plasticity.
authors.affiliation: Department of Biochemistry, Biophysics, & Molecular Biology, Iowa State University, Ames, Iowa 50011, USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Criswell
authors.forename: Kevin
authors.initials: K
authors.lastname: Potter
authors.forename: Freya
authors.initials: F
authors.lastname: Shephard
authors.forename: Michael H
authors.initials: MH
authors.lastname: Beale
authors.forename: Reuben J
authors.initials: RJ
authors.lastname: Peters
mesh_terms: D028202:Abies / Q000201:enzymology; D001224:Aspartic Acid / Q000737:chemistry / Q000235:genetics; D002384:Catalysis; D003500:Cyclization; D004224:Diterpenes / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D006639:Histidine / Q000737:chemistry / Q000235:genetics; D006900:Hydroxylation; D007535:Isomerases / Q000145:classification / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D010755:Organophosphates / Q000737:chemistry / Q000378:metabolism*; D011106:Polyisoprenyl Phosphates / Q000737:chemistry
chemical_list: D004224:Diterpenes; D010755:Organophosphates; D011106:Polyisoprenyl Phosphates; C408747:copalyl diphosphate; D001224:Aspartic Acid; D006639:Histidine; D007535:Isomerases; C088741:abietadiene cyclase; C002963:geranylgeranyl pyrophosphate