Prephenate dehydratase (PDT)

Prephenate dehydratase (PDT) is a key enzyme in the shikimate pathway, responsible for the biosynthesis of the essential amino acid L-phenylalanine in bacteria, fungi, and plants [1, 10]. It catalyzes the conversion of prephenate to phenylpyruvate through a combined dehydration and decarboxylation reaction [2, 11]. In many Gram-negative bacteria, PDT is part of a bifunctional enzyme called the P-protein, which also exhibits chorismate mutase activity [1, 3]. Because the shikimate pathway and PDT are entirely absent in humans and other mammals, the enzyme is considered a highly attractive target for the development of novel antibiotics and herbicides [10, 13]. Targeting PDT allows for the selective inhibition of pathogen growth by depriving them of an essential nutrient without affecting human metabolic processes [10, 16]. Although no PDT inhibitors are currently approved for clinical use, research has identified several experimental compounds, such as biphenic acid derivatives and nitrobenzoates, that show potent inhibitory activity [8]. These inhibitors typically act by competing with the substrate or through allosteric mechanisms, as the enzyme is naturally regulated by L-phenylalanine [10, 14]. Future development of PDT-targeted therapies could provide a new class of narrow-spectrum antimicrobials to combat the rising threat of multi-drug resistant infections [16, 18].

Other names

Prephenate hydro-lyase (decarboxylating)Chorismate mutase-prephenate dehydrataseP-proteinPheA

Inhibition of L-phenylalanine biosynthesis by blocking the conversion of prephenate to phenylpyruvate, leading to bacterial growth inhibition [10, 19].