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.

Vanadium containing bromoperoxidase – Insights into the enzymatic mechanism using X-ray crystallography

“…In addition this group also demonstrated that the indole was binding to the active site as evidenced by fluorescence quenching. Furthermore, the same enzyme will catalyse a regiospecific indole bromination [24]. These results again are direct evidence that the reaction is occurring within the enzyme catalytic site.…”

51V NMR Chemical Shifts Calculated from QM/MM Models of Vanadium Chloroperoxidase

“…[1][2][3][4][5] The controlled partial oxidation of such substrates to well-defined products is potentially very useful.…”

Haloperoxidase Enzymes as ‘Redox Catalysts’ Important for Industrial Biocatalysis

“…Nonetheless, the same group has demonstrated that the indole was binding directly to the active site as shown by fluorescence quenching experiments. Furthermore, the A. nodosum bromoperoxidase enzyme was shown to catalyze a regiospecific indole bromination reaction (Martinez et al 2001). These results provide direct evidence that the reaction is occurring within the enzyme active site.…”