Chemistry and Redox Biology of Mycothiol.

TitleChemistry and Redox Biology of Mycothiol.
Publication TypeJournal Article
Year of Publication2018
AuthorsReyes, A. M., B. Pedre, M. Inés De Armas, M-A. Tossounian, R. Radi, J. Messens, and M. Trujillo
JournalAntioxid Redox Signal
Date Published2018 02 20
KeywordsCysteine, Glycopeptides, Inositol, Mycobacterium tuberculosis, Oxidants, Oxidation-Reduction, Oxidative Stress, Peroxidases, Sulfhydryl Compounds

SIGNIFICANCE: Mycothiol (MSH, AcCys-GlcN-Ins) is the main low-molecular weight (LMW) thiol of most Actinomycetes, including the human pathogen Mycobacterium tuberculosis that affects millions of people worldwide. Strains with decreased MSH content show increased susceptibilities to hydroperoxides and electrophilic compounds. In M. tuberculosis, MSH modulates the response to several antituberculosis drugs. Enzymatic routes involving MSH could provide clues for specific drug design. Recent Advances: Physicochemical data argue against a rapid, nonenzymatic reaction of MSH with oxidants, disulfides, or electrophiles. Moreover, exposure of the bacteria to high concentrations of two-electron oxidants resulted in protein mycothiolation. The recently described glutaredoxin-like protein mycoredoxin-1 (Mrx-1) provides a route for catalytic reduction of mycothiolated proteins, protecting critical cysteines from irreversible oxidation. The description of MSH/Mrx-1-dependent activities of peroxidases helped to explain the higher susceptibility to oxidants observed in Actinomycetes lacking MSH. Moreover, the first mycothiol-S-transferase, member of the DinB superfamily of proteins, was described. In Corynebacterium, both the MSH/Mrx-1 and the thioredoxin pathways reduce methionine sulfoxide reductase A. A novel tool for in vivo imaging of the MSH/mycothiol disulfide (MSSM) status allows following changes in the mycothiol redox state during macrophage infection and its relationship with antibiotic sensitivity.CRITICAL ISSUES: Redundancy of MSH with other LMW thiols is starting to be unraveled and could help to rationalize the differences in the reported importance of MSH synthesis observed in vitro versus in animal infection models.FUTURE DIRECTIONS: Future work should be directed to establish the structural bases of the specificity of MSH-dependent enzymes, thus facilitating drug developments. Antioxid. Redox Signal. 28, 487-504.

Alternate JournalAntioxid. Redox Signal.
PubMed ID28372502
Research group: