ABSTRACT

Mycothiol (MSH) is the major low-molecular-weight thiol in actinomycetes and has glutathione as analogous molecule in eukaryotes and gram-negative bacteria. This chapter presents MSH and its molecular partners, providing a general perspective on its protective mechanism and pathways. MSH is composed of N-acetyl l-cysteine, d-glucosamine, and 1-d-myo-inositol, linked by an amide bond between the carboxyl group of N-acetyl l-cysteine and the amino group of the d-glucosamine moiety, which is connected with a glycosidic bond to 1-d-myo-inositol. The MSH-biosynthetic pathway consists of five unique steps catalyzed by different enzymes, glucosamine transferase (MshA), MshA2, MshB, MshC, and MshD. MSH biosynthesis begins with the conversion of uridine diphosphate N-acetyl glucosamine into 1-O-(2-acetoamido-2-deoxy-a-d-glucopyranolyl)-d-myo-inositol-3-phosphate by an N-acetyl-MshA. The mshA-deficient strain had an impaired growth rate in the initial phase and a remarkably lethal phenotype when exposed to hydrogen peroxide, gaseous nitric oxide, iodoacetamide, 1-chloro-2,4-dinitrobenzene, and other antibiotics such as rifamycin, streptomycin, erythromycin, and azithromycin.