VANADIUM 581

K02 VANADIUM BROMOPEROXIDASE: ENZYME AND BIOMIMETIC INVESTIGATIONS

Alison Butler, M.J. Clague, G.E. Meister, R.A. Tschirret-Guth, and J.V. Walker Department o]:Chernistry, University of California, Santa Barbara, CA 93106 USA

Many halogenated compounds have been isolated from marine organisms, including halogenated indoles and terpenes. The biosynthesis of these compounds is thought to be mediated by haloperoxidases. Vanadium bromoperoxidase (V-BrPO) is an enzyme isolated primarily from marine algae that catalyzes peroxidative halogenation reactions and the halide-assisted disproportionation of hydrogen peroxide, forming dioxygen. The nature of the oxidized halogen intermediate as enzyme-bound or released depends on the nature of the organic substrate. Indoles bind to V-BrPO blocking the release of a diffusible oxidized bromine intermediate [1]. The kinetics and mechanism of indole bromination by the V-BrPO system differs from chemical bromination by HOBr/Br2/Br3- species. Other organic substrates also bind to V-BrPO and thus the selectivity of V-BrPO can be directed by the nature of the organic

H202 Br-

aE ~ ~ ""EBr" j

substrate.

E + "HOBr = Br2 = Br3-"

,, S binding H202

Br-S 102 Br-S

Vanadium can be removed from V-BrPO producing the inactive apoprotein derivative; the activity can be fully restored by addition of vanadate to apo-BrPO. While few spectroscopic techniques permit observation of the vanadium site during turnover, biomimetic studies have helped to establish the role of the essential vanadium(V) ion. The first functional mimic of V-BrPO, cis-dioxovanadium(V) (VO2 +) coordinates hydrogen peroxide forming the mono and diperoxo-vanadium(V) species. Neither VO(O2) ÷ nor VO(Oz)2- can oxidize bromide directly, but rather dimerize producing (VO)2(O2)3, the active oxidant of bromide [2]. Some mononuclear liganded complexes of vanadium and other transition metal ions also catalyze peroxidative halogenation reactions, although the rates of oxidation of bromide by these systems and VO2 + are significantly slower than V-BrPO. Thus clearly the protein ligand plays an important role.

1. Tschirret-Guth, R.A., Butler, A., J. Am. Chem. Soc. 1994, 116, 411-412. 2. Clague, M.J., Butler, A., J. Am. Chem. Soc., 1995, 117 In press. Acknowledgements: AB is grateful for support from NSF, California Sea Grant and NIH for enzyme and model compound studies.