Hung-wen Liu

Mechanistic Studies of HPP Epoxidase: Configuration of the Substrate Governs Its Enzymatic Fate

Non-heme iron-dependent enzymes are an important class of catalysts involved in many biological transformations of medical, pharmaceutical, and environmental significance. Although considerable progress has been made in our understanding of their catalyses, characterization of the metal centers and the modes of dioxygen activation remain a challenge because of the great structural and mechanistic diversity found among these enzymes.[1] Recently, HPP epoxidase,[2] an enzyme in the biosynthetic pathway of the antibiotic fosfomycin, was recognized as a new member of this enzyme family.[3] This epoxidase performs the final transformation in the fosfomycin biosynthesis by converting (S)-2hydroxypropylphosphonic acid (HPP, (S)-1) to (1R,2S)-epoxypropylphosphonic acid (2), also known as fosfomycin COMMUNICATIONS