Characterization of thiamine pyrophospho kinase of vitamin B1 biosynthetic pathway as a drug target in Lesishmania donovani

Vitamin B1 is an essential cofactor required by carbohydrate-metabolizing enzymes such as Transketolases. Humans obtain these vitamins from their diet, although certain bacteria, yeast, plants, and lower eukaryotes synthesize them de novo . Because of the specificity of this system, the enzymes involved are amenable to therapeutic manipulation. In the final step of Thiamin Pyrophosphate (TPP) biosynthetic pathway, Thiamine Pyrophospho Kinase (TPK) converts Thiamin into its active form, TPP, opening an avenue to investigate the functional importance of this enzyme and the pathway's dispensability in Leishmania donovani , a protozoan parasite that causes visceral leishmaniasis. ldtpk gene encodes a 545 amino acid protein with a molecular mass of 58.4 kDa. Ld TPK over-expression, antibody generation, cellular localization, enzyme kinetics, and inhibition assays with Oxythiamin and Pyrithiamin may provide a sound platform for the discovery of potential inhibitors for this enzyme. As a result, an in-depth analysis of the enzymes involved in TPP biosynthesis in L. donovani has the potential to generate novel therapeutic strategies for Leishmaniasis.