Dihydropteroate synthase (Propionibacterium acnes) (DHPS)

Dihydropteroate synthase (DHPS) is a fundamental enzyme in the bacterial de novo folate biosynthesis pathway, responsible for catalyzing the reaction between para-aminobenzoic acid (PABA) and 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate to produce 7,8-dihydropteroate (UniProt EC 2.5.1.15). In the bacterium Propionibacterium acnes (recently reclassified as Cutibacterium acnes), this enzyme serves as the molecular target for sulfonamide antibiotics and the sulfone drug dapsone (Ross et al., 1997; Scholz & Kilian, 2016). These drugs function as competitive inhibitors of DHPS, effectively halting the production of dihydrofolate and subsequently inhibiting DNA synthesis and bacterial growth. Because humans lack the DHPS enzyme and rely on dietary folate, it is a highly selective target for treating conditions like acne vulgaris. However, the increasing prevalence of sulfonamide resistance in C. acnes, often mediated by specific point mutations in the folP gene encoding DHPS, presents a significant challenge to current therapeutic strategies (Lomholt & Kilian, 2010).

Other names

7,8-dihydropteroate synthaseDihydropteroate pyrophosphorylasefolPCutibacterium acnes dihydropteroate synthaseP. acnes DHPS

Competitive inhibition of dihydropteroate synthase (DHPS) by structural mimicry of p-aminobenzoic acid (PABA), leading to the inhibition of folate biosynthesis.