Inhibitors of Mycothiol-S-Conjugate Amidase and Related Genes

Mycothiol is a small molecular weight thiol exclusive to actinomycetes, a subgroup of Gram-positive bacteria. Mycothiol is composed of one unit each of 1-D-glucosamine, 1-D-myo-inositol and N-acetyl cysteine. Novel enzymes involved in mycothiol biosynthesis, mycothiol-mediated detoxification, and mycothiol reduction have recently been identified, and several of these share little or no sequence homology to known mammalian enzymes. Together, these points suggest that targeting of mycothiol-associated biochemistry may be a valid approach to identifying new types of antibiotics specific to actinomycetes, which include the medically important mycobacteria. This review discusses mycothiol literature to date, with emphasis on chemical approaches to identifying and synthesizing inhibitors and chemical probes to study mycothiol biochemistry.