InterPro domain: IPR004561

Isochorismate synthase ( 5.4.99.6 ) catalyses the conversion of chorismate to isochorismate, the first step in the biosynthesis of both the respiratory chain component menaquinone (MK, vitamin K2) and phylloquinone (vitamin K1). In bacteria, isochorismate is a precursor of siderophores enterobactin (via the 2,3-dihydroxybenzoate (DHB) precursor) [ 1 ], amonabactins [ 2 ] and salicylic acid [ 3 ]. Most aerobic bacteria secrete siderophores to facilitate iron acquisition [ 4 ]. Siderophores are iron-chelating agents which are low molecular weight compounds that specifically bind ferric iron and mediate iron uptake into the cell by recognition of specific membrane receptor proteins and transport systems. In plants, isochorismate synthase is required for defence against pathogens. Salicylic acid synthesised via the pathway using isochorismate synthase is responsible for both local and systemic acquired resistance in plants [ 5 ].

In Escherichia coli and Bacillus subtilis, two distinct isochorismate synthase isoenzymes, MenF [ 6 ] and EntC [ 7 ]/DhbC [ 7 ], are known to be involved in MK and siderophore biosynthesis pathways, respectively [ 8 ]. MenF and EntC are differentially regulated and isochorismate synthesised by EntC is mainly channelled into enterobactin synthesis, whereas isochorismate synthesised by MenF is mainly channelled into menaquinone synthesis [ 9 ].

The catalytic/chorismate binding domain characteristic of members of this group is related to other chorismate binding enzymes [ 10 ]: component I of anthranilate synthase, para-aminobenzoate synthase, and aminodeoxychorismate synthase (please see PIRSF001373 and PIRSF001374 ).

There is a significant heterogeneity in the length and sequence of the N-terminal region of members of this group. Partially on the basis of the N-terminal region, the group can be divided into subfamilies, with the enzymes involved in DHB (enterobactin precursor) biosynthesis (EntC/DhbC/VibC) forming a distinct subfamily, and the enzymes involved in MK biosynthesis (MenF) forming two groups (E. coli and B. subtilis types).

1. Overexpression, purification, and characterization of isochorismate synthase (EntC), the first enzyme involved in the biosynthesis of enterobactin from chorismate. Biochemistry 29, 1417-25
2. Cloning, mutagenesis, and nucleotide sequence of a siderophore biosynthetic gene (amoA) from Aeromonas hydrophila. J. Bacteriol. 173, 5121-8
3. Structural genes for salicylate biosynthesis from chorismate in Pseudomonas aeruginosa. Mol. Gen. Genet. 249, 217-28
4. Self-assembling amphiphilic siderophores from marine bacteria. Science 287, 1245-7
5. Isochorismate synthase is required to synthesize salicylic acid for plant defence. Nature 414, 562-5
6. A new isochorismate synthase specifically involved in menaquinone (vitamin K2) biosynthesis encoded by the menF gene. FEMS Microbiol. Lett. 140, 159-63
7. Duplicate isochorismate synthase genes of Bacillus subtilis: regulation and involvement in the biosyntheses of menaquinone and 2,3-dihydroxybenzoate. J. Bacteriol. 178, 854-61
8. An isochorismate hydroxymutase isogene in Escherichia coli. FEBS Lett. 378, 131-4
9. Clustering of isochorismate synthase genes menF and entC and channeling of isochorismate in Escherichia coli. Biochim. Biophys. Acta 1522, 151-7
10. The crystal structure of anthranilate synthase from Sulfolobus solfataricus: functional implications. Proc. Natl. Acad. Sci. U.S.A. 96, 9479-84