Molecular Biology, Genetics and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria.
Biochem Soc Trans. 2022 Feb 28;50(1):335-345. doi: 10.1042/BST20210506.
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 biochemical activities. Yeast-derived enzyme D-amino acid oxidase (DAAO) represents the first of its kind for a substrate-based chemogenetic approach to modulate H2O2 concentrations within cells. Combining these powerful enzymes with multiparametric imaging methods exploiting genetically encoded biosensors has opened new lines of investigations in life sciences. In recent years, 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 covers established or emerging methods and assesses newer approaches exploiting chemogenetic tools combined with genetically encoded biosensors.
化学生物学工具是重组酶，可以靶向特定的细胞器和组织。提供或去除酶的底物可以控制其生化活性。酵母来源的酶 D-氨基酸氧化酶（DAAO）代表了基于底物的化学生物学方法的首例，可调节细胞内 H2O2 浓度。将这些强大的酶与利用基因编码生物传感器的多参数成像方法相结合，为生命科学的研究开辟了新的途径。近年来，化学生物学 DAAO 方法已被证明有助于在培养细胞和动物模型系统中确立（病理）生理氧化应激在基于氧化还原的信号转导和代谢途径中的新作用。这篇小型综述涵盖了已建立或新兴的方法，并评估了利用化学生物学工具与基因编码生物传感器相结合的新方法。
