Isochorismate-utilizing enzymes (IUEs)

Isochorismate-utilizing enzymes (IUEs) are a diverse group of enzymes, primarily found in bacteria, fungi, and plants, that catalyze the conversion of isochorismate into various essential metabolites. This group includes enzymes such as isochorismatase, isochorismate pyruvate lyase, and bifunctional salicylate synthases like MbtI, which are central to the biosynthesis of siderophores (iron-chelating molecules), menaquinone (an electron carrier in the respiratory chain), and salicylic acid (a key signaling molecule in plant immunity). Because the metabolic pathways involving isochorismate are absent in humans, IUEs are considered highly attractive and selective targets for the development of novel antimicrobial agents, particularly against Mycobacterium tuberculosis and other multidrug-resistant pathogens. Inhibitors of these enzymes, such as furan-based compounds and transition state analogs, aim to disrupt iron acquisition or energy metabolism in the pathogen, effectively starving the microorganism or halting its growth. While many experimental inhibitors show potent in vitro activity, therapeutic development faces challenges related to bacterial cell wall permeability and the pharmacological profiles of lead compounds in vivo.

Other names

MST family enzymesIsochorismate synthaseSalicylate synthaseIsochorismataseIsochorismate pyruvate lyaseMbtIMenDEntBPchBDhbC

Inhibition of siderophore production (iron starvation), Inhibition of menaquinone biosynthesis (disruption of electron transport), Disruption of iron acquisition, Disruption of energy metabolism