Ethylene Biosynthesis by 1-Aminocyclopropane-1-Carboxylic Acid Oxidase: A DFT Study

The reaction catalyzed by the plant enzyme 1‐aminocyclopropane‐1‐carboxylic acid oxidase (ACCO) was investigated by using hybrid density functional theory. ACCO belongs to the non‐heme iron(II) enzyme superfamily and carries out the bicarbonate‐dependent two‐electron oxidation of its substrate ACC (1‐aminocyclopropane‐1‐carboxylic acid) concomitant with the reduction of dioxygen and oxidation of a reducing agent probably ascorbate. The reaction gives ethylene, CO2, cyanide and two water molecules. A model including the mononuclear iron complex with ACC in the first coordination sphere was used to study the details of OO bond cleavage and cyclopropane ring opening. Calculations imply that this unusual and complex reaction is triggered by a hydrogen atom ion step generating a radical on the amino nitrogen of ACC. Subsequently, cyclopropane ring opening followed by OO bond heterolysis leads to a very reactive iron(IV)–oxo intermediate, which decomposes to ethylene and cyanoformate with very low energy barriers. The reaction is assisted by bicarbonate located in the second coordination sphere of the metal. New insight into the mechanism of 1‐aminocyclopropane‐1‐carboxylic acid oxidation at the active site of 1‐aminocyclopropane‐1‐carboxylic acid oxidase is provided by density functional studies described herein. The active site of the enzyme, as well as the products, are shown in the graphic.