Guidelines for tunneling in enzymes

Here we extend the engineering descriptions of simple, single-electron-tunneling chains common in oxidoreductases to quantify sequential oxidation–reduction rates of two-or-more electron cofactors and substrates. We identify when nicotinamides may be vulnerable to radical mediated oxidation–reduction and merge electron-tunneling expressions with the chemical rate expressions of Eyring. The work provides guidelines for the construction of new artificial oxidoreductases inspired by Nature but adopting independent design and redox engineering.