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Folic acid biosynthesis pathway enzyme (in bacteria)

Molecular classification
Enzyme, Metabolic pathway (composed of multiple enzymes, e.g., GTP cyclohydrolase I, dihydropteroate synthase, dihydrofolate reductase)
01

Overview

The folic acid biosynthesis pathway in bacteria is a metabolic pathway essential for the synthesis of tetrahydrofolate (THF) and related folates, which serve as one-carbon donors in nucleotide and amino acid biosynthesis as well as other key cellular processes[2][4][6]. This pathway is present in bacteria but not in mammals, making it an attractive target for antibacterial drug development[2][4]. Multiple enzymes catalyze sequential steps, including GTP cyclohydrolase I, dihydropteroate synthase, and dihydrofolate reductase[2][4][5]. Inhibitors of this pathway include sulfonamides (which mimic PABA and inhibit dihydropteroate synthase) and trimethoprim (which inhibits dihydrofolate reductase)[3][5]. Resistance commonly arises through mutations in these enzymes or increased PABA production[3]. Disruption of folate synthesis impairs bacterial DNA, RNA, and protein synthesis, ultimately inhibiting bacterial growth and replication[5]. Note: There is something incorrect with the target as given. "Folic acid pathway in bacteria" refers to a multi-enzyme metabolic pathway, not a single canonical molecular target. When detailing therapeutic targets, it is more precise to refer to a specific enzyme within this pathway, such as "Dihydrofolate reductase (DHFR)" or "Dihydropteroate synthase (DHPS)"[2][4]. As such, "Folic acid pathway in bacteria" should be flagged as too broad/vague for a canonical molecular target; individual pathway enzymes are the actual drug targets.

Other names
Folate pathwayBacterial folate synthesis pathway
02

Mechanism of action

Inhibition of dihydropteroate synthase (by sulfonamides, blocking PABA incorporation)[3]; Inhibition of dihydrofolate reductase (by trimethoprim, preventing tetrahydrofolate synthesis)[3]

03

Biological functions

Nucleotide biosynthesisAmino acid biosynthesisMethylation reactions (via one-carbon metabolism)Essential bacterial metabolism
04

Disease associations

Infection (bacterial)Other (Antimicrobial resistance)
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Safety considerations

Gut microbiota disruption due to impaired bacterial folate metabolismEmergence of resistance (mutations in target enzymes, overproduction of PABA)[3]
06

Interacting drugs

Sulfonamides (e.g. sulfamethoxazole, sulfadiazine, sulfadoxine)

2 more in the full profile.

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