title: Mycothiol biochemistry.
abstract: Mycothiol (MSH) is a novel thiol comprised of N-acetylcysteine amide-linked to GlcN-alpha(1-1)-Ins. It is the major thiol in most actinomycetes and is produced at millimolar levels in mycobacteria and streptomycetes. MSH biosynthesis occurs by linkage of GlcNAc to Ins, deacetylation to GlcN-Ins, ligation of the latter to L-cysteine, and transacetylation of the cysteinyl residue by CoASAc to produce MSH. The genes encoding the respective enzymes have been designated mshA, mshB, mshC, and mshD; all but mshA have been identified. Mycobacterium smegmatis mutants deficient in mshA, mshC, and mshD have been characterized. MSH plays a significant role in the detoxification of thiol-reactive substances, including formaldehyde, various electrophiles, and antibiotics. Mycothiol S-conjugates derived from electrophiles and antibiotics are cleaved by mycothiol S-conjugate amidase to release GlcN-Ins, used to resynthesize MSH, and a mercapturic acid which is excreted from the cell. A mycothiol-disulfide-selective reductase has been identified and likely helps to maintain cellular MSH in the reduced state. Mycothiol biochemistry has characteristics similar to those of glutathione but also has a variety of unique features.
authors.affiliation: Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, CA 92093-0506, USA.
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Newton
authors.forename: Robert C
authors.initials: RC
authors.lastname: Fahey
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000581:Amidohydrolases / Q000378:metabolism; D003545:Cysteine; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D006020:Glycopeptides; D008658:Inactivation, Metabolic / Q000502:physiology*; D007294:Inositol; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000235:genetics; D010084:Oxidation-Reduction; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004187:Disaccharides; D006020:Glycopeptides; D011720:Pyrazoles; D013438:Sulfhydryl Compounds; C089265:mycothiol; D007294:Inositol; D000445:Aldehyde Oxidoreductases; C108807:mycothiol-dependent formaldehyde dehydrogenase; D000581:Amidohydrolases; C413523:mycothiol S-conjugate amidase; D003545:Cysteine