title: On the regiospecificity of vanadium bromoperoxidase.
abstract: Vanadium haloperoxidase enzymes catalyze the oxidation of halide ions by hydrogen peroxide, producing an oxidized intermediate, which can halogenate an organic substrate or react with a second equivalent of hydrogen peroxide to produce dioxygen. Haloperoxidases are thought to be involved in the biogenesis of halogenated natural products isolated from marine organisms, including indoles and terpenes, of which many are selectively oxidized or halogenated. Little has been shown concerning the ability of the marine haloperoxidases to catalyze regioselective reactions. Here we report the regiospecific bromoperoxidative oxidation of 1,3-di-tert-butylindole by V-BrPO from the marine algae Ascophyllum nodosum and Corallina officinalis. Both enzymes catalyze the regiospecific oxidation of 1,3-di-tert-butylindole in a reaction requiring both H(2)O(2) and Br(-) as substrates, but which produce the unbrominated 1,3-di-tert-butyl-2-indolinone product exclusively, in near quantitative yield (i.e. one H(2)O(2) consumed per product). By contrast, reactions with the controlled addition of aqueous bromine solution (HOBr = Br(2) = Br(3)(-)) produce three monobromo and one dibromo-2-indolinone products, all of which differ from the V-BrPO-catalyzed product. Further, reactivities of 1,3-di-tert-butyl-2-indolinone with both aqueous bromine and V-BrPO differ significantly and shed light onto the possible nature of the oxidizing intermediate. This is the first example of a regiospecific bromination by a vanadium haloperoxidase and further extends their usefulness as catalysts.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106-9510, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Martinez
authors.forename: G L
authors.initials: GL
authors.lastname: Carroll
authors.forename: R A
authors.initials: RA
authors.lastname: Tschirret-Guth
authors.forename: G
authors.initials: G
authors.lastname: Altenhoff
authors.forename: R D
authors.initials: RD
authors.lastname: Little
authors.forename: A
authors.initials: A
authors.lastname: Butler
mesh_terms: D001667:Binding, Competitive; D001966:Bromine / Q000737:chemistry / Q000378:metabolism; D007211:Indoles / Q000737:chemistry*; D007700:Kinetics; D010544:Peroxidases / Q000737:chemistry / Q000378:metabolism*; D000459:Phaeophyceae / Q000201:enzymology*; D010637:Phenolsulfonphthalein / Q000737:chemistry / Q000378:metabolism; D000461:Rhodophyta / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: C434340:1,3-di-tert-butylindole; D007211:Indoles; D010544:Peroxidases; C026195:bromide peroxidase; D010637:Phenolsulfonphthalein; D001966:Bromine