The maintenance of thiol-redox homeostasis is vital to the survival of living organisms. Sulfur-based low-molecular weight compounds and proteins synthesized by cells provide efficient and specific ways to counteract oxidative stress and regulate cellular processes. For these tasks, most organisms share the glutathione and thioredoxin NADPH-dependent redox systems. However, in certain lineages, evolution has taken different paths that led to the emergence of novel cysteine-based low-molecular weight redox cofactors, around which new redox systems evolved. These include the sugar-based cysteinyl derivatives mycothiol and bacillithiol, and ergothioneine (EGT), which are present in different phyla from bacteria. Within Eukarya, some fungi contain EGT, whereas trypanothione is unique to species from the Euglenozoa family. This Forum compiles the state-of-the-art knowledge about these noncanonical redox systems of pathogenic organisms. The functions in physiology and pathogenicity, as well as structural and biochemical specializations that these system components evolved, are thoroughly discussed. Antioxid. Redox Signal. 28, 407-409.
Keywords: bacillithiol; ergothioneine; mycothiol; trypanothione.