Chemogenetic approaches to dissect the role of H2O2 in redox-dependent pathways using genetically encoded biosensors

Chemogenetic tools are recombinant enzymes that can be targeted to specific organelles and tissues. The provision or removal of the enzyme substrate permits control of its bio-chemical activities. Yeast-derived enzyme D-amino acid oxidase (DAAO) represents the first of its kind for a substrateoased chemogenetic approach to modulate H2O2 concen-trations within cells. Combining these powerful enzymes with multiparametric imaging methods exploiting genetically encoded biosensors has opened new lines of investiga-tions in life sciences. In recent year s , the chemogenetic DAAO approach has proven beneficial to establish a new role for (patho)physiological oxidative stress on redox-dependent signaling and metabolic pathways in cultured cells and animal model systems. This mini-review cover s established or emerging methods and assesses newer approaches exploiting chemogenetic tools combined with genetically encoded biosensors.