Tyrosinase Catalyzes Asymmetric Sulfoxidation

• Published in: Biochemistry (Easton) Vol. 47; no. 11; pp. 3493 - 3498
• Main Authors: Pievo, Roberta, Gullotti, Michele, Monzani, Enrico, Casella, Luigi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.03.2008
• Subjects: Agaricus - enzymology; Catalysis; Fungal Proteins - chemistry; Fungal Proteins - metabolism; Hydroxylation; Levodopa - chemistry; Levodopa - metabolism; Monophenol Monooxygenase - chemistry; Monophenol Monooxygenase - metabolism; Oxidation-Reduction; Substrate Specificity; Sulfides - chemistry; Sulfides - metabolism; Sulfoxides - chemistry; Sulfoxides - metabolism
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi702421b

Mushroom tyrosinase was found to catalyze the oxidation of organic sulfides to sulfoxides in the presence of a catechol as cosubstrate, in a reaction which is unprecedented for this enzyme and resembles those performed by external monooxygenases. Only the oxy form of the enzyme is in fact capable of oxidizing the sulfide in a two-electron process, while the resulting met form can only be recycled by reduction with catechol. The cosubstrate competes with the sulfide also in the reaction with oxy-tyrosinase. For this reason, the sulfoxidation of thioanisole in the presence of l-3,4-dihydroxyphenylalanine (L-dopa) occurs with moderate yields (∼20%) but high enantioselectivity (∼85% e.e.), and favors (S)-methyl phenyl sulfoxide. The enantioselectivity can be further increased to >90% when excess ascorbic acid is added to the reaction to limit enzyme inactivation by the quinones produced by L-dopa oxidation. An experiment using 18O2 showed that 18-O incorporation into methyl phenyl sulfoxide was above 95%, confirming that the mechanism of the sulfoxidation involves oxygen transfer from oxy-tyrosinase to the sulfide.