Isochorismate synthase (ICS)

Isochorismate synthase is an intramolecular transferase enzyme (EC 5.4.4.2) that catalyzes the isomerization of chorismate to isochorismate, a key step in the biosynthesis of diverse and essential metabolites across bacteria, archaea, fungi, and plants[2][4][1][3][8]. In bacteria (e.g., *E. coli*), it provides precursors for menaquinone and siderophore production (notably, by the isoforms MenF and EntC), vital for electron transport and iron acquisition[1][2][8]. In plants, isoforms such as ICS1 and ICS2 catalyze the committed step toward salicylic acid production, a phytohormone critical for plant immune responses, and also contribute to the biosynthesis of phylloquinone (vitamin K1)[5][6][7][8]. The enzyme has a well-characterized magnesium-dependent mechanistic pathway, with its activity and regulation elucidated by structural biology in recent years[3][5]. Isochorismate synthase is a promising target for antibacterial drug development and metabolic engineering, though no approved therapeutics currently exist. It also serves as a key node in both primary and specialized metabolism, with potential as a biomarker in plant and microbial biology[8][4][7][6][5][2][1][3].

Other names

Isochorismate synthase 1 (ICS1)Isochorismate synthase 2 (ICS2)EntC (E. coli gene product for siderophore biosynthesis)MenF (E. coli gene product for menaquinone biosynthesis)AtICS1, AtICS2 (Arabidopsis thaliana orthologs)PchA (Pseudomonas aeruginosa isoform for pyochelin biosynthesis)

Inhibition of catalytic conversion of chorismate to isochorismate, thereby blocking biosynthesis of the respective end product (e.g., salicylic acid, siderophores, menaquinone) Mg²⁺-dependent enzyme mechanism is key; drugs may chelate Mg²⁺ or compete at the active site