Here the "Molecular Lego" approach was used to achieve the first reported electrochemical signal of human CYP2A6 and to improve its catalytic efficiency on electrode surfaces. The enzyme was fused at the genetic level to flavodoxin from Desulfovibrio vulgaris(FLD) to create the chimeric CYP2A6-FLD. Electrochemical characterization by cyclic voltammetry shows clearly defined redox transitions of the haem domain in both CYP2A6 and CYP2A6-FLD.Electrocatalysis experiments using coumarin as substrate followed by fluorimetric quantification of the product were performed with immobilised CYP2A6 and CYP2A6-FLD. Comparison of the kinetic parameters showed that coumarin catalysis was carried out with a higher efficiency by the immobilised CYP2A6-FLD, with a calculated kcat value significantly higher (P<0.005) than that of CYP2A6, while the affinity for the substrate (KM) remained unaltered. The chimeric system was also successfully used to demonstrate the inhibition of the electrochemical activity of the immobilised CYP2A6-FLD, towards both coumarin and nicotine substrates, by tranylcypromine, a potent and selective CYP2A6 inhibitor.This work shows that CYP2A6 turnover efficiency is improved when the protein is linked to FLD redox module and this strategy can be utilized for the development of new clinically relevant biotechnological approaches suitable for deciphering the metabolic implications of CYP2A6 polymorphism and for the screening of CYP2A6 substrates and inhibitors.