Tyrosinase Catalyzed Asymmetric Sulfoxidation

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 (Ldopa)
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.