*3.3. Modification of Carbon Nanomaterials with Substrate Mimics*

Compared to nonspecific electrostatic and hydrophobic interactions, interactions between redox enzymes and their natural substrates are usually highly specific. A more effective approach is the direct functionalization of carbon nanomaterials with a natural substrate (or its analogues) of redox enzymes to control the orientation of the redox enzymes. A significant improvement in the O2-reduction current has been realized through the adsorption of *Mv*BOD in bilirubin, the natural substrate of *Mv*BOD, which is a functionalized KB electrode [65]. (Figure 5C) A computational study that combines the density functional theory with docking simulations showed that the modification of the electrode surface with bilirubin provides an optimal orientation of BOD toward the support and that bilirubin facilitates the interfacial electron transfer by decreasing the distance between the electrode surface and the T1 Cu atom [66]. Similar improvements in DET-type bioelectrocatalysis can be realized through the adsorption of *Mv*BOD at 2,5-dimethyl-1-phenyl-1H-pyrrole-3-carbaldehyde [67], syringaldazine [68], or protoporphyrin [69], analogues of bilirubin, and functionalized CNT electrodes. Syringaldazine-functionalized CNTs were also shown to be positively effective in improving the interfacial electron transfer of laccase [68]. Moreover, an improved DET-type bioelectrocatalysis of FDH at a methoxy-functionalized electrode surface [70] based on the specific interactions between FDH and methoxy substituents [8] has been reported. The fructose oxidation current produced by FDH at 2,4-dimethoxyaniline-functionalized KB electrodes reached to 23 ± 2 mA cm−<sup>2</sup> , which is the largest measured to date. A recent study proposed that 4-mercaptopyridine functionalized gold nanoparticle-embedded KB can act as a favorable platform for DET-type bioelectrocatalysis of FoDH [71], probably owing to the attractive interactions between the pyridine moiety and the FeS site of FoDH. These results suggest that site-specific interactions are also effective in inducing a suitable orientation of redox enzymes for DET-type bioelectrocatalysis.
