Shikimate pathway

The shikimate pathway is a conserved, seven-step metabolic pathway found in bacteria, archaea, fungi, algae, some protozoa, and plants, but absent in animals[1][2][3][5][6][8]. It catalyzes the conversion of phosphoenolpyruvate and erythrose 4-phosphate into chorismate, a critical branch-point precursor for the biosynthesis of the aromatic amino acids phenylalanine, tyrosine, and tryptophan[1][2][4][5][6][7][8]. Chorismate, and various intermediates of the pathway, serve as the basis for the production of numerous natural products including certain vitamins, cofactors, metabolites (such as flavonoids, alkaloids, and lignin), and specialized secondary metabolites[1][3][6][7][9]. All steps in the pathway are catalyzed by specific enzymes, many of which are themselves drug targets. Since animals (including humans) lack the shikimate pathway, its enzymes are attractive targets for antimicrobials and herbicides[2][3][8]. Glyphosate, a widely used herbicide, acts by inhibiting the EPSPS enzyme within this pathway, effectively blocking aromatic amino acid biosynthesis and leading to plant death[2][3][5][9]. The pathway is also the focus of research into antibiotic development, as its absence from animals provides a rationale for selective toxicity[8]. Regulatory mechanisms of the shikimate pathway differ between organisms but commonly involve feedback inhibition and gene expression control[1][5][6]. While it is not a single molecular target (such as a receptor or enzyme), but rather a pathway comprised of multiple enzyme targets, the shikimate pathway remains a central node for therapeutic intervention in agriculture (weed control) and anti-infectives[8]. Caveat: The shikimate pathway—as a term—does not refer to a single "receptor" or "protein," but to a series of enzymes and their catalyzed reactions; in drug discovery, targets are typically individual enzymes within this pathway (e.g., EPSPS), but the pathway itself is commonly referred to as a therapeutic target in plants and microbes[2][3][8].

Other names

Shikimic acid pathwayChorismate biosynthesis pathway

Inhibition of pathway enzymes, especially 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) by competitive inhibition (e.g., glyphosate)[2][3][5][8].