Isochorismate synthase

Isochorismate synthase (MenF) (EC number 5.4.4.2) catalyzes the first step in the biosynthesis of vitamin K (menaquinone) in Escherichia coli.[1]

Isochorismate synthase
Ishochorismate Synthase cartoon view (2 subunits)
Identifiers
EC number	5.4.4.2
CAS number	37318-53-9
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Search PMC articles PubMed articles NCBI proteins

Reaction

Isochorismate synthase is an enzyme that catalyzes the irreversible conversion of chorismate to isochorismate:

Isochorismate synthase is most active at 37 °C and at a pH between 7.5 and 8. It requires Mg²⁺ as a cofactor, in a concentration between 100 μM and 1 mM.[1] Inhibitors of isochorismate synthase include:

• (4R,5R)-4-hydroxy-5-(1-carboxyvinyloxy)-cyclohex-1-ene carboxylate
• (4R,5R)-4-hydroxy-5-carboxymethoxy-cyclohex-1-enecarboxylate
• (4R,5R)-5-(2-carboxy-allyloxy)-4-hydroxy-cyclohex-1-enecarboxylate
• (4R,5R,6S)-6-ammonio-5-[(1-carboxylatoethenyl)oxy]-4-hydroxycyclohex-1-ene-1-carboxylate
• (4R,5R,7R)-5-(1-carboxy-ethoxy)-4-hydroxy-cyclohex-1-enecarboxylate
• (4R,5R,7S)-5-(1-carboxy-ethoxy)-4-hydroxy-cyclohex-1-enecarboxylate
• (4R,5S,6S)-4-ammonio-5-[(1-carboxylatoethenyl)oxy]-6-hydroxycyclohex-1-ene-1-carboxylate
• (4R,5S,6S)-5-[(1-carboxylatoethenyl)oxy]-4,6-dihydroxycyclohex-1-ene-1-carboxylate[2]
• Cu²⁺
• Hg²⁺
• K⁺
• Mg²⁺ at concentrations above 1 mM
• NEM

Nomenclature

Isochorismate synthase, or MenF, belongs to the isomerase enzyme family. More specifically it is classified as an intramolecular transferase because it transfers the hydroxy group of chorismate between carbons.[3] The systematic name of this enzyme is isochorismate hydroxymutase, and the common name is isochorismate synthase. Other names for this enzyme include:

• Isochorismate mutase
• Menaquinone-specific isochorismate synthase
• MenF

Vitamin K

Vitamin K contains a quinone ring that participates in redox reactions. These reactions take place in various organisms such as plants, where electrons are transferred during photosynthesis, humans, where electrons are transferred to modify certain types of proteins, and bacteria, where electrons are transferred during anaerobic respiration.[4]

Pathways

MenF is a gene that codes for the isochorismate synthase found in the menaquinone pathway in Escherichia coli, not to be mistaken for the entC gene that codes for the isochorismate synthase found in the enterobacter pathway in Escherichia coli.[1] Isochorismate synthase has several other homologs that are found in other organisms. These include:

Enzyme Genes/Enzyme Names	Organisms
ICS	Arabidopsis thaliana Cyanidium caldarium Glycine max Nicotiana benthamiana Populus fremontil Populus angustifolia Populus tremuloides
ICS1	Arabidopsis thaliana
ICS1 gene product	Arabidopsis thaliana Cyanidium caldarium
ICS2	Arabidopsis thaliana
Isochorismate synthase	Arabidopsis thaliana Cyanidium caldarium Glycine max
Isochorismate synthase 1	Arapidopsis thaliana
Mbtl	Mycobacterium tuberculosis
PchA	Pseudomonas aeruginosa

References

1. Daruwala R, Bhattacharyya DK, Kwon O, Meganathan R (May 1997). "Menaquinone (vitamin K2) biosynthesis: overexpression, purification, and characterization of a new isochorismate synthase from Escherichia coli". Journal of Bacteriology. 179 (10): 3133–8. doi:10.1128/jb.179.10.3133-3138.1997. PMC 179089. PMID 9150206.
2. Payne RJ, Bulloch EM, Toscano MM, Jones MA, Kerbarh O, Abell C (June 2009). "Synthesis and evaluation of 2,5-dihydrochorismate analogues as inhibitors of the chorismate-utilising enzymes". Organic & Biomolecular Chemistry. 7 (11): 2421–9. doi:10.1039/B901694E. PMID 19462053.
3. "EC 5.4.4.2". IUBMB. Retrieved 30 November 2014.
4. van Oostende C, Wildhalm JR, Furt F, Ducluzeau AL, Basset GJ (2011). "Phylloquinone (Vitamin K2): function,enzymes and genes". Advances in Botanical Research: 229–61.