Shikimate kinase (SK)

Shikimate kinase (SK) is an essential enzyme in the shikimate pathway, which is responsible for the biosynthesis of aromatic amino acids—phenylalanine, tyrosine, and tryptophan—in bacteria, fungi, and plants [1, 2]. It catalyzes the fifth step of this pathway, specifically the ATP-dependent phosphorylation of the 3-hydroxyl group of shikimate to produce shikimate-3-phosphate [4, 13]. Because the shikimate pathway is entirely absent in mammals, who must obtain these amino acids through their diet, SK has emerged as a highly attractive target for the development of selective antimicrobial and antitubercular agents [3, 10]. Inhibition of this enzyme leads to a deficiency in critical amino acids, effectively halting protein synthesis and impairing the survival of pathogens like Mycobacterium tuberculosis [2, 4]. Research into SK inhibitors has identified various chemical scaffolds, including benzothiazoles, benzimidazoles, and natural alkaloids, which aim to provide new treatments for multidrug-resistant infections [7, 14]. While no SK-targeted drugs are currently FDA-approved, the enzyme remains a focal point for rational drug design due to its essentiality and the potential for minimal toxicity in human hosts [1, 11].

Other names

ATP:shikimate 3-phosphotransferaseAroKAroLShikimate 3-phosphotransferaseShikimate kinase IShikimate kinase II

Competitive or non-competitive inhibition of the enzyme, blocking the conversion of shikimate to shikimate-3-phosphate and disrupting the biosynthesis of essential aromatic amino acids [2, 14].