Archives of Microbiology

, Volume 178, Issue 6, pp 388–394 | Cite as

Mycothiol biochemistry

  • Gerald L. Newton
  • Robert C. Fahey
Mini-Review

Abstract.

Mycothiol (MSH) is a novel thiol comprised of N-acetylcysteine amide-linked to GlcN-α(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. Electronic Supplementary Material is available if you access this article at http://dx.doi.org/10.1007/s00203-002-0469-4. On that page (frame on the left side), a link takes you directly to the supplementary material.

Mycothiol mshA, mshB mshC mshD mca mtr Mycobacterium tuberculosis Antibiotic detoxification Mercapturic acid 

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Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Gerald L. Newton
    • 1
  • Robert C. Fahey
    • 1
  1. 1.Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093–0506, USA

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