3-Dehydroquinate synthase (DHQS)

Molecular Classification

Enzyme, Lyase (specifically: EC 4.2.3.4)

Other Names

Dehydroquinate synthase, DHQS, AROM protein (as part of the AROM complex in some eukaryotes)

Disease Roles

Infection (targeted in antimicrobial, antifungal, anti-parasitic drug discovery)Other (herbicidal target)

3-Dehydroquinate synthase Overview

3-Dehydroquinate synthase is a monomeric enzyme (about 37–39 kDa) that catalyzes the second step in the shikimate pathway—a biosynthetic route essential for the production of aromatic amino acids such as phenylalanine, tyrosine, and tryptophan—in bacteria, plants, fungi, and some protists, but absent in animals and humans. It converts 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) to 3-dehydroquinate through a complex mechanism involving oxidation, phosphate elimination, carbonyl reduction, ring opening, and aldol condensation. The essential nature of the shikimate pathway in many pathogens, and its absence in mammals, makes 3-dehydroquinate synthase an attractive and highly selective target for antimicrobial, antifungal, anti-parasitic, and herbicidal development. In some fungi and protists, this enzyme forms part of a larger multifunctional protein complex known as the AROM complex. Enzyme activity requires cofactors such as NAD+, and may depend on divalent metal ions (notably Co2+, Zn2+, Mn2+, or Cd2+ in some species)[1][5][6][8][9]. **Note:** No approved drugs currently target this enzyme in clinical practice, but research is ongoing in the context of new antimicrobial and herbicidal agents. No human biomarker or safety concern exists given humans lack the shikimate pathway[1][6].

Mechanism of Action

Inhibition of the enzyme to block the shikimate pathway, thereby preventing biosynthesis of aromatic amino acids and leading to growth inhibition or death of bacteria, fungi, or plants[1][4][6].

Biological Functions

Biosynthesis of aromatic amino acids

Catalysis in the shikimate pathway

Precursor supply for secondary metabolites in plants, bacteria, and fungi

Disease Associations

Infection (targeted in antimicrobial, antifungal, anti-parasitic drug discovery)

Other (herbicidal target)

Safety Considerations

Off-target effects in non-target organisms (relevant for herbicide development)
Resistance development in microbes (potential)
Not directly applicable to humans due to absence of the shikimate pathway, which is a safety advantage for antimicrobials[1][6].

Interacting Drugs

No approved drugs currently known to target specifically 3-dehydroquinate synthase in clinical use; however, molecule classes considered include antimicrobial, antifungal, anti-parasitic, and herbicidal inhibitors targeting this enzyme[1][4][6].