A novel reduction-stress elimination system by the Escherichia coli DsbA and its application to L-cysteine production

DsbA将肽基l -半胱氨酸残基氧化为外周质中的二硫桥，还原后的DsbA被细胞膜蛋白DsbB再氧化。从泛醌得到的电子被给予DsbA。最后，氧通过呼吸链末端氧化酶（DsbA-DsbB-UQ复合物）成为电子受体。我们发现，DsbA通常是氧化形式，在添加过量的Cys时，以还原形式的DsbA移位。此外，作为DsbA底物之一的OstA蛋白是大肠杆菌生长所必需的蛋白质，它也以还原形式积累到外周质中。我们认为dsba - dsbb -泛醌氧化系统可能通过氧化外源还原剂来消除还原性应激，并在细胞质的氧化还原稳态中发挥重要作用。类似于大肠杆菌dsba - dsbb -泛醌氧化系统的机制也广泛存在于酵母、植物、动物等的内质网和线粒体中。这是与生物类的毒性相对应的。

DsbA oxidizes peptidyl L-cysteine residue into disulfide bridge in the periplasm, and the reduced form of DsbA is re-oxidized by inner membrane protein DsbB. Electron, which is received from ubiquinone, is given to DsbA. Finally, oxygen is an electron acceptor through the terminal oxidase of the respiratory chain (DsbA-DsbB-UQ complex). We find that DsbA, which is normally the oxidized form, is shifted in the reduced form of DsbA in the addition of excess Cys. Furthermore, OstA protein, which is one of the DsbA substrates and is an essential protein for Escherichia coli growth, is also accumulated as reduced form into the periplasm. We suggested that the DsbA-DsbB-ubiquinone oxidation system might eliminate reductive stress by oxidizing exogenous reductants and also play an important role in redox homeostasis in the cytoplasm. A similar mechanism to DsbA-DsbB-ubiquinone oxidation system of E. coli exists widely also in endoplasmic reticulum of yeast, the plant, and the animal, etc. and mitochondria. This is corresponding to the toxicity of Cys that exceeds the living thing kind.