Mycobacterium leprae dihydropteroate synthase (DHPS)

Mycobacterium leprae dihydropteroate synthase (DHPS), encoded by the folP1 gene, is a vital enzyme in the de novo folate biosynthesis pathway of the leprosy-causing bacterium (UniProt P0C0X1). It catalyzes the reaction between 6-hydroxymethyl-7,8-dihydropterin pyrophosphate and para-aminobenzoic acid (PABA) to produce 7,8-dihydropteroate. Since humans lack this biosynthetic pathway and must obtain folate through their diet, DHPS is a highly selective target for antimicrobial therapy. Dapsone, a primary component of the World Health Organization's multidrug therapy (MDT) for leprosy, functions by competitively inhibiting this enzyme. However, the clinical utility of dapsone is increasingly threatened by the emergence of resistant strains harboring specific point mutations in the folP1 gene, particularly at codons 53 and 55 (Williams et al., 2000, Antimicrob Agents Chemother). Monitoring these genetic markers is essential for the surveillance of drug-resistant leprosy and for guiding effective treatment regimens. Beyond resistance, the use of drugs targeting this enzyme requires careful management of side effects such as hemolytic anemia and hypersensitivity reactions.

Other names

FolP17,8-dihydropteroate synthaseDihydropteroate pyrophosphorylaseDihydropteroate synthase 1

Competitive inhibition of the enzyme by acting as a structural analog of para-aminobenzoic acid (PABA), which prevents the condensation of PABA with 6-hydroxymethyl-7,8-dihydropterin pyrophosphate, thereby blocking the synthesis of dihydropteroate and subsequent folate production (PubChem, CID 2955).