The Mechanism of Human Aromatase (CYP 19A1) Revisited: DFT and QM/MM Calculations Support a Compound I-Mediated Pathway for the Aromatization Process

Human aromatase is responsible for the last step of estrogen biosynthesis, for the aromatization of ring A of androstenedione (ASD) or testosterone. In this work the mechanism of aromatization was studied using gas phase and hybrid QM/MM calculations. It is shown that human aromatase can efficiently catalyze the aromatization process via a Compound I (or Compound II) mediated pathway. The nature of the oxidant is very sensitive to the polarizing environment of the enzyme, as the oxidant has a Compound I nature in the gas phase * corresponding author, to whom corresponding should be addressed e-mail: [email protected]; telephone number: +36-1-463-1286