Graphitic materials exhibit significant anisotropy due to the difference in conductivity in a single layer and between adjacent layers. This anisotropy is manifested on epitaxial graphene (EG), which can be manipulated on the nanoscale in order to provide tailor-made properties. Insertion of defects into the EG lattice was utilized here for controllable surface modification with a model biocatalyst and the properties were quantified by both electrochemical and optical methods. A comparative evaluation of the electrode reaction kinetics on the enzyme-modified 2D material vs conventional carbon electrode materials revealed a significant enhancement of mediated bioelectrocatalysis at the nanoscale.