Hydrogen peroxide is a substrate or side-product in many enzyme-catalyzed reactions. For example, it is a side-product of oxidases,
resulting from the re-oxidation of FAD with molecular oxygen, and it is a substrate for peroxidases and other enzymes. However,
hydrogen peroxide is able to chemically modify the peptide core of the enzymes it interacts with, and also to produce the oxidation of
some cofactors and prostetic groups (e.g., the hemo group). Thus, the development of strategies that may permit to increase the stability
of enzymes in the presence of this deleterious reagent is an interesting target. This enhancement in enzyme stability has been attempted
following almost all available strategies: site-directed mutagenesis (eliminating the most reactive moieties), medium engineering (using
stabilizers), immobilization and chemical modification (trying to generate hydrophobic environments surrounding the enzyme, to confer
higher rigidity to the protein or to generate oxidation-resistant groups), or the use of systems capable of decomposing hydrogen peroxide
under very mild conditions. If hydrogen peroxide is just a side-product, its immediate removal has been reported to be the best solution.
In some cases, when hydrogen peroxide is the substrate and its decomposition is not a sensible solution, researchers coupled one enzyme
generating hydrogen peroxide “in situ” to the target enzyme resulting in a continuous supply of this reagent at low concentrations thus
preventing enzyme inactivation.
This review will focus on the general role of hydrogen peroxide in biocatalysis, the main mechanisms of enzyme inactivation produced
by this reactive and the different strategies used to prevent enzyme inactivation caused by this “dangerous liaison”.