Prephenate dehydrogenase (PDH)

Prephenate dehydrogenase (PDH) is a critical enzyme in the shikimate pathway, responsible for the oxidative decarboxylation of prephenate to 4-hydroxyphenylpyruvate, a key intermediate in the biosynthesis of L-tyrosine [1, 3]. This enzyme is found in bacteria, fungi, and plants but is notably absent in mammals, making it a highly attractive target for the development of narrow-spectrum antibiotics and herbicides with minimal host toxicity [12, 20]. In many enteric bacteria, PDH exists as a bifunctional enzyme (T-protein) fused with chorismate mutase, whereas in other pathogens like Mycobacterium tuberculosis and Bacillus anthracis, it functions as a monofunctional protein [20, 25]. PDH activity is typically regulated by feedback inhibition from L-tyrosine, which binds to regulatory domains such as the ACT domain to allosterically inhibit the enzyme [5, 25]. Targeting PDH offers a strategic approach to combat multidrug-resistant infections by disrupting essential amino acid production without affecting human metabolic pathways [20, 22]. Additionally, the enzyme plays a role in the biosynthesis of secondary metabolites, including antibiotics like novobiocin and chloramphenicol [3].

Other names

TyrAPrephenate:NAD+ oxidoreductase (decarboxylating)Hydroxyphenylpyruvate synthaseCyclohexadienyl dehydrogenaseChorismate mutase-prephenate dehydrogenase

Inhibition of L-tyrosine biosynthesis via the shikimate pathway