Dihydropteroate synthase (DHPS) is an enzyme classified under . It catalyzes a condensation reaction:
(2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate + 4-aminobenzoate (PABA) diphosphate + dihydropteroate.
This reaction produces dihydropteroate. DHPS is found in archaea, bacteria, some protozoans, fungi, and plants, but not in animals. In non-archaeal organisms, this enzyme participates in folate biosynthesis. In archaea, this enzyme participates in methanopterin biosynthesis. All organisms require a reduced folate/methanopterin cofactor for their one-carbon metabolism. Most microorganisms must synthesize folate de novo because they lack the active transport system of animal cells that allows these organisms to use preformed folates.
The nonexistence of DHPS in humans (and its essential role in other organisms) makes it a useful target for sulfonamide antibiotics, which compete with the PABA precursor (see dihydropteroate synthase inhibitor). All organisms require reduced folate cofactors
Examples Bacterial DHPS (gene sul or folP) is a protein of about 275 to 315 amino acid residues that is either chromosomally encoded or found on various antibiotic resistance plasmids.
In the fungus Pneumocystis jirovecii (previously P. carinii) DHPS is the C-terminal domain of a multifunctional folate synthesis enzyme (gene fas) with 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase (HPPK). A similar arrangement is found in the model plant Arabidopsis thaliana.https://enzyme.expasy.org/EC/2.5.1.15 (specifically, in IUBMB commentary). DHPS is the target of the herbicide asulam.
The Saccharomyces cerevisiae (baker's yeast, a fungus) version is trifunctional: the enzyme has DHPS, HPPK, and dihydroneopterin aldolase.
Protein domain
Proteins containing the pterin-binding enzyme domain include dihydropteroate synthase () as well as a group of methyltransferase enzymes including 5-Methyltetrahydrofolate:corrinoid/iron-sulfur protein Co-methyltransferase (MeTr) that catalyses a key step in the Wood-Ljungdahl pathway of carbon dioxide fixation.
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