title: Ergothioneine protects Streptomyces coelicolor A3(2) from oxidative stresses.
abstract: Thiol compounds with low-molecular weight, such as glutathione, mycothiol (MSH), bacillithiol, and ergothioneine (ERG), are known to protect microorganisms from oxidative stresses. Mycobacteria and actinobacteria utilize both MSH and ERG. The biological functions of MSH in mycobacteria have been extensively studied by genetic and biochemical studies, which have suggested it has critical roles for detoxification in cells. In contrast, the biological functions of ERG remain ambiguous because its biosynthetic genes were only recently identified in Mycobacterium avium. In this study, we constructed mutants of Streptomyces coelicolor A3(2), in which either the MSH or ERG biosynthetic gene was disrupted, and examined their phenotypes. A mshC (SCO1663)-disruptant completely lost MSH productivity. In contrast, a disruptant of the egtA gene (SCO0910) encoding γ-glutamyl-cysteine synthetase unexpectedly retained reduced productivity of ERG, probably because of the use of l-cysteine instead of γ-glutamyl-cysteine. Both disruptants showed delayed growth at the late logarithmic phase and were more susceptible to hydrogen peroxide and cumene hydroperoxide than the parental strain. Interestingly, the ERG-disruptant, which still kept reduced ERG productivity, was more susceptible. Furthermore, the ERG-disruptant accumulated 5-fold more MSH than the parental strain. In contrast, the amount of ERG was almost the same between the MSH-disruptant and the parental strain. Taken together, our results suggest that ERG is more important than MSH in S. coelicolor A3(2).
authors: Graduate School of Engineering, Hokkaido University, Hokkaido 060-8628, Japan.
authors: Shunsuke
authors: S
authors: Nakajima
authors: Graduate School of Engineering, Hokkaido University, Hokkaido 060-8628, Japan.
authors: Yasuharu
authors: Y
authors: Satoh
authors: Kyowa Hakko Bio Co. Ltd., Chiyoda-ku, Tokyo 100-8185, Japan.
authors: Kentaro
authors: K
authors: Yanashima
authors: Graduate School of Engineering, Hokkaido University, Hokkaido 060-8628, Japan.
authors: Tomomi
authors: T
authors: Matsui
authors: Graduate School of Engineering, Hokkaido University, Hokkaido 060-8628, Japan. Electronic address: dairi@eng.hokudai.ac.jp.
authors: Tohru
authors: T
authors: Dairi
mesh_terms: D003545:Cysteine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism; D004880:Ergothioneine / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D006020:Glycopeptides / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000494:pharmacology; D007294:Inositol / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D048372:Streptomyces coelicolor / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
chemical_list: D006020:Glycopeptides; C089265:mycothiol; D007294:Inositol; D006861:Hydrogen Peroxide; D004880:Ergothioneine; D005721:Glutamate-Cysteine Ligase; D003545:Cysteine
keywords: Biological function; Ergothioneine; Mycothiol; Oxidative stress; Streptomyces coelicolor