Subsystem: Menaquinone and Phylloquinone Biosynthesis
This subsystem's description is:
Menaquinone (MK; vitamin K2)is derived from the common branch-point intermediate, chorismate, of the shikimate pathway in bacteria. It is a lipid-soluble molecule that serves important biological functions. In most anaerobes and all Gram-positive aerobes, menaquinone is the sole electron transporter in the respiratory chain and is essential for their survival. It also serves as an electron carrier in facultative Gram-negative aerobes, such as Escherichia coli, but only during their anaerobic growth. In contrast, menaquinone is a vitamin (K2) in humans and animals; it plays a totally different role, serving as an enzyme cofactor involved in glutamate -carboxylation that is essential in blood clotting. Due to its absence in humans and animals, menaquinone biosynthesis is an appealing target for development of antibiotics for pathogenic microbes that depend on the naphthoquinone for survival, such as Mycobacterium tuberculosis.
Menaquinone differs from phylloquinone by the presence of a partly unsaturated, predominantly C-40 side chain rather than a mostly saturated, C-20 phytol side chain. With this exception, the synthesis of the naphthalene nucleus in phylloquinone and menaquinone is expected to include similar steps.
Phylloquinone (vitamin K) is found mainly in green plants and plays an important function in blood coagulation.
The genes encoding the enzymes involved in the conversion of chorismate to menaquinone have been cloned in Escherichia coli and Bacillus subtilis.
Six genes, designated menA, -B, -C, -D, -E, and -F, have been implicated in the biosynthesis of MK from chorismate and 2-ketoglutarate. Five of these, menB, -C, -D, -E, and -F, all clustered at 51 min on the Escherichia coli chromosome, are responsible for the conversion of chorismate and 2-ketoglutarate to the soluble naphthalenoid aromatic compound 1,4-dihydroxy-2-naphthoic acid (DHNA). In a subsequent reaction, the DHNA is attached to the membrane-bound octaprenylpyrophosphate and results in the formation of demethylmenaquinone (DMK by the product of gene menA ( see Diagram).
1.0 - Organisms, containing the complete set of all Menaquinone and Phylloquinone Biosynthesis genes (see diagram);
1.x – Organisms, which definitely have the Menaquinone and Phylloquinone Biosynthesis but some genes in the pathway are missed. Mostly thise is gene ubiE coding two methyltransferases on the last 2 steps of the pathway. In Anabaena variabilis ATCC 29413 and in Trichodesmium erythraeum IMS101 the absense of menB should be caused by very uncomplete genome. Same - for Crocosphaera watsonii WH 8501 (315 contigs).;
2.0 - Organisms (Mycobacterium and Corynebacterium ) missing the first step enzyme- menF-Menaquinone-specific isochorismate synthase (EC 18.104.22.168);
(-1) – no Menaquinone or Phylloquinone Biosynthesis ( as in Saccharomyces cerevisiae); gene ubiE is shown in some of these organisms because it’s product-Ubiquinone/menaquinone biosynthesis methyltransferase UbiE/COQ5 (EC 2.1.1.-) - participates in Ubiquinone biosynthesis as well.
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|Literature References||Identification and characterization of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase in the menaquinone biosynthesis of Escherichia coli. Jiang M Biochemistry 2008 Mar 18||18284213||Menaquinone biosynthesis in Escherichia coli: identification of 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate as a novel intermediate and re-evaluation of MenD activity. Jiang M Biochemistry 2007 Sep 25||17760421||Biosynthesis of menaquinone (vitamin K2) and ubiquinone (coenzyme Q): a perspective on enzymatic mechanisms. Meganathan R Vitamins and hormones 2001||11153266||Menaquinone (vitamin K2) biosynthesis: localization and characterization of the menA gene from Escherichia coli. Suvarna K Journal of bacteriology 1998 May||9573170||Evolution of structure and function in the o-succinylbenzoate synthase/N-acylamino acid racemase family of the enolase superfamily. Glasner ME Journal of molecular biology 2006 Jun 30||16740275|
|Diagram||Functional Roles||Subsystem Spreadsheet||Description||Additional Notes||Scenarios|