folP

folP is the gene that encodes dihydropteroate synthase (DHPS), an enzyme in the folate biosynthesis pathway of many bacteria and some archaea. DHPS catalyzes the condensation of p-aminobenzoic acid (pABA) with dihydropteridine pyrophosphate to form dihydropteroate, a key precursor that leads to dihydrofolate and ultimately tetrahydrofolate, which are essential cofactors for thymidylate and purine synthesis.

The gene is widespread among organisms that synthesize folate de novo and is commonly found in bacterial genomes, often within operons dedicated to folate metabolism. DHPS is not present in animals that obtain folate from their diet, reflecting differences in folate biosynthesis across domains of life. Because of its central role, folP is typically essential under conditions requiring de novo folate production.

Clinically and biotechnologically, folP is noteworthy as the target of sulfonamide antibiotics, which inhibit DHPS and disrupt folate synthesis in susceptible organisms. Resistance to sulfonamides can arise through mutations in folP that reduce drug binding, acquisition of resistant folP alleles, or increased gene dosage. Such resistance mechanisms can complicate treatment and are an area of ongoing surveillance in pathogenic bacteria.

Structurally, DHPS is a cytosolic enzyme that functions as a dimer in many organisms, with a typical size of about 260–320 amino acids per monomer. Its active site binds pABA and the pteridine-derived substrate, and the enzyme’s activity can be affected by mutations that alter substrate binding or catalytic efficiency.

In summary, folP encodes a pivotal enzyme in bacterial folate biosynthesis, with significant implications for antibiotic action and resistance, and it serves as a model for studying enzyme inhibition in metabolic pathways.