Carbonic anhydrase binds a zinc ion in a hydrophobic active site using the imidazole groups of three histidine residues. The natural role of carbonic anhydrase is to catalyze the reversible hydration of carbon dioxide to bicarbonate, but it also catalyzes hydrolysis of esters with moderate enantioselectivity. Replacing the active-site zinc with manganese yielded manganese-substituted carbonic anhydrase (CA[Mn]), which shows peroxidase activity with a bicarbonate-dependent mechanism. In the presence of bicarbonate and hydrogen peroxide, CA[Mn] catalyzed the efficient oxidation of o-dianisidine with kcat/ KM = 1.4 × 106M-1s-1. which is comparable to that for horseradish peroxidase, kcat/ KM/KM = 57 × 106M-1 s-1. CA[Mn] also catalyzed the moderately enantioselective epoxidation of olefins to epoxides (E =5 for p-chlorostyrene). This enantioselectivity is similar to that for natural heme-based peroxidases, but has the advantage that CA[Mn] avoids formation of aldehyde side products. CA[Mn] degrades during the epoxidation, limiting the yield of the epoxidations to <12%. Replacement of active-site residues Asn62, His64, Asn67, Gln92, or Thr200 with alanine by site-directed mutagenesis decreased the enantioselectivity showing that the active site controls enantioselectivity of the epoxidation.