**3. SAMs and Electrochemical DET of Redox Proteins**/**Enzymes**

SAMs have received considerable early and recent attention as substrates for interfacial bioelectrochemical DET reactions, and a wide range of metalloproteins have been investigated in terms of catalytic mechanism and ET kinetics on various SAM-modified electrode surfaces. The redox active centers of protein/enzymes in DET can be roughly categorized into two major groups: metal-based (iron, copper and molybdenum centers etc.) [20,69–71] and non-metal-based (e.g., flavin adenine dinucleotide (FAD) and pyrrolo-quinoline quinone (PQQ)) centers [44,72,73]. Most, although not all, DET-capable enzymes harbor multiple redox centers, with internal ET relays via heme groups, copper clusters, or Fe-S clusters, which shuttle electrons between the electrode surface and the catalytic cofactors [45,74,75]. In this section, we overview recent studies where SAMs have been used in DET-type electrocatalysis and discuss how to obtain favorable orientations using versatile SAMs, as well as how to tune the interactions between the redox protein/enzyme and the SAM-modified electrodes. Redox proteins/enzymes which can be immobilized in well-defined orientations on SAM-modified supports are illustrated in Figure 2 [4,15,19,32,64,67,70,76–81]. We shall overview and discuss some selected examples from each of these enzyme classes in Sections 3.1–3.3.

**Figure 2.** (**a**) Illustration of common proteins/enzymes capable of direct electron transfer (DET) on electrode modified by self-assembled molecular monolayers (SAMs). The proteins include: horse heart cytochrome *c* (cyt *c*), PDB 1HRC; cellobiose dehydrogenase (CDH) from *Neurospora crassa*, PDB 4QI7; gamma-alpha subunit of FAD-dependent glucose dehydrogenase (FAD-GDH) from *Burkholderia cepacia*, PDB 6A2U; chicken liver sulfite oxidase (SOx), PDB 1SOX; *Pseudomonas aeruginosa* azurin T30R1, PDB 5I28; monomer of *Achromobacter xylosoxidans* copper nitrite reductase (*Ax*CuNiR), PDB 1HAU; bilirubin oxidase from *Myrothecium verrucaria* (BOD), PDB 2XLL; laccase (Lac) from *Trametes versicolor*, PDB 1KYA; [NiFe]-hydrogenase from *DesulfovVibrio Vulgaris* Miyazaki F (*Dv*MF), PDB 1UBU. Schematic view of representative DET processes of (**b**) *mv*BOD and (**c**) SOx on the electrode modified with negatively and positively charged SAMs, respectively.
