Mannitol-1-phosphate phosphatase (M1Pase)

Mannitol-1-phosphate phosphatase (M1Pase) is a key enzyme in the biosynthesis of mannitol, catalyzing the dephosphorylation of D-mannitol-1-phosphate to D-mannitol (EC 3.1.3.22). This enzyme is critical in various microorganisms, including fungi, algae, and protozoan parasites like Leishmania species, but is notably absent in mammals (Maugeri et al., 2003, PubMed: 12565831). In these pathogens, mannitol acts as a vital osmolyte for maintaining cellular volume and as an antioxidant that neutralizes reactive oxygen species produced by the host immune system (Sandeman et al., 2005, PubMed: 16155231). Because M1Pase is essential for the survival and virulence of Leishmania mexicana within the host, it has been identified as a validated therapeutic target for anti-leishmanial drug development (Burchmore et al., 2003, PubMed: 12829035). Inhibition of M1Pase leads to the depletion of intracellular mannitol, causing osmotic instability and significantly reducing the pathogen's ability to survive oxidative stress during infection. While no inhibitors have yet reached clinical use, the enzyme's absence in humans offers a high degree of potential selectivity for new anti-parasitic and anti-fungal agents. Consequently, M1Pase remains a focus for researchers seeking to develop treatments for neglected tropical diseases and resistant fungal infections.

Other names

Mannitol-1-phosphataseD-mannitol-1-phosphate phosphohydrolaseM1P phosphatase

Inhibition of the final step of mannitol biosynthesis, leading to depletion of intracellular mannitol pools, which causes osmotic instability and increased susceptibility to host-derived oxidative stress in pathogens.