If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: superpathway of demethylmenaquinone-6 biosynthesis
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Quinol and Quinone Biosynthesis → Demethylmenaquinol Biosynthesis → Demethylmenaquinol-6 Biosynthesis|
Some taxa known to possess this pathway include : Haemophilus parainfluenzae
Expected Taxonomic Range: Haemophilus
Menaquinones (MK) and demethylmenaquinones (DMK) are low-molecular weight lipophilic components of the cytoplasmic membrane, found in many bacterial species. These quinones function as a reversible redox component of the electron transfer chain, mediating electron transfer between hydrogenases and cytochromes. Menaquinones have also been implicated in regulation, as they are necessary for sporulation and proper regulation of cytochrome formation in some Gram-positive bacteria [Farrand73, Farrand74].
Most aerobic Gram-negative bacteria contain ubiquinone as the sole quinone, while most aerobic Gram-positive bacteria contain menaquinone and/or demethylmenaquinones as the main quinone. However, most of the anaerobic bacteria, regardless whether they are Gram-negative or Gram-positive, contain menaquinone or demethylmenaquinone as their main quinones. Some facultatively anaerobic bacteria, such as Escherichia coli, contain ubiquinone, menaquinone, and demethylmenaquinone, which they use under different growth conditions [Meganathan01a]. The main difference between these quinone molecules is their redox potential. For example, the redox potential for ubiquinone, demethylmenaquinone, and menaquinone has been measured as +112 mv, +36 mv, and -74 mv, respectively, in the bacterium Haemophilus parainfluenzae [Hollander76].
Menaquinones are considered a vitamin (vitamin K2), since they are essential for animals, mostly for the posttranslational modification of certain proteins required for blood coagulation. Animals can not synthesize menaquinones, but usually receive a sufficient amount from bacteria growing in their intestines. In the absence of menaquinone or the related compound phylloquinone (vitamin K1) which is synthesized in plants, animals suffer from hemorrhage [Dam35]. Menaquinone was first isolated from putrefied fish meal by McKee in 1939 [Doisy40], and its structure resolved in 1958 [Isler58].
The biosynthesis of menaquinones is essentially identical to that of demethylmenaquinones, with one additional step, comprising the addition of a methyl group to the naphthoquinone ring. Many bacterial species do not have this methylase and produce demethylmenaquinone as their sole quinone [Collins81].
All three quinones are synthesized from chorismate, an intermediate of aromatic amino acid biosynthesis. However, the pathways of (demethyl)menaquinone synthesis diverts from that for ubiquinones early on. Most organisms synthesize their menaquinones via isochorismate, although some organisms, including Helicobacter pylori, Campylobacter jejuni, Streptomyces coelicolor and Thermus thermophilus, synthesize menaquinones in alternative pathways, via futalosine or 6-amino-6-deoxyfutalosine [Hiratsuka08, Li11, Goble13].
About This Pathway
In this pathway menaquinone is synthesized from chorismate via isochorismate. In a series of reactions, isochorismate is converted to the two-ring compound 1,4-dihydroxy-2-naphthoate via several intermediates that include 2-succinylbenzoate. At this point a prenyltransferase enzyme attaches a polyprenyl tail to form a demethylmenaquinone, which can be converted to a menaquinone by a dedicated methylase.
Demethylquinones were first discovered in Haemophilus parainfluenzae [Lester64]. The main form was demethylmenaquinone-6 (DMK-6), although lesser amounts of DMK-5 and DMK-7 were also detected. Additional studies found that DMK-6 is involved in respiration in Haemophilus parainfluenzae, and could mediate electron transfer between NADH and succinate, similar to ubiquinone (Q). In addition, DMK-6 could act as a mediator in fumarate reduction, similar to menaquinone (MK). Thus, in contrast to Q and MK, DMK acts equally well in succinate respiration and in fumarate reduction [Hollander76].
Fujimoto12: Fujimoto N., Kosaka T., Yamada M. (2012). "Menaquinone as Well as Ubiquinone as a Crucial Component in the Escherichia coli Respiratory Chain." Chapter 10 in Chemical Biology, edited by D Ekinci, ISBN 978-953-51-0049-2.
Goble13: Goble AM, Toro R, Li X, Ornelas A, Fan H, Eswaramoorthy S, Patskovsky Y, Hillerich B, Seidel R, Sali A, Shoichet BK, Almo SC, Swaminathan S, Tanner ME, Raushel FM (2013). "Deamination of 6-aminodeoxyfutalosine in menaquinone biosynthesis by distantly related enzymes." Biochemistry 52(37);6525-36. PMID: 23972005
Hiratsuka08: Hiratsuka T, Furihata K, Ishikawa J, Yamashita H, Itoh N, Seto H, Dairi T (2008). "An alternative menaquinone biosynthetic pathway operating in microorganisms." Science 321(5896);1670-3. PMID: 18801996
Li11: Li X, Apel D, Gaynor EC, Tanner ME (2011). "5'-methylthioadenosine nucleosidase is implicated in playing a key role in a modified futalosine pathway for menaquinone biosynthesis in Campylobacter jejuni." J Biol Chem 286(22);19392-8. PMID: 21489995
Ashby90: Ashby MN, Edwards PA (1990). "Elucidation of the deficiency in two yeast coenzyme Q mutants. Characterization of the structural gene encoding hexaprenyl pyrophosphate synthetase." J Biol Chem 265(22);13157-64. PMID: 2198286
Bhasin03: Bhasin M, Billinsky JL, Palmer DR (2003). "Steady-state kinetics and molecular evolution of Escherichia coli MenD [(1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase], an anomalous thiamin diphosphate-dependent decarboxylase-carboligase." Biochemistry 42(46);13496-504. PMID: 14621995
Bhattacharyya97: Bhattacharyya DK, Kwon O, Meganathan R (1997). "Vitamin K2 (menaquinone) biosynthesis in Escherichia coli: evidence for the presence of an essential histidine residue in o-succinylbenzoyl coenzyme A synthetase." J Bacteriol 1997;179(19);6061-5. PMID: 9324253
Chen11a: Chen M, Jiang M, Sun Y, Guo ZF, Guo Z (2011). "Stabilization of the second oxyanion intermediate by 1,4-dihydroxy-2-naphthoyl-coenzyme A synthase of the menaquinone pathway: spectroscopic evidence of the involvement of a conserved aspartic acid." Biochemistry 50(26);5893-904. PMID: 21627110
Chen13a: Chen M, Ma X, Chen X, Jiang M, Song H, Guo Z (2013). "Identification of a Hotdog Fold Thioesterase Involved in the Biosynthesis of Menaquinone in Escherichia coli." J Bacteriol 195(12);2768-75. PMID: 23564174
Dahm98: Dahm C, Muller R, Schulte G, Schmidt K, Leistner E (1998). "The role of isochorismate hydroxymutase genes entC and menF in enterobactin and menaquinone biosynthesis in Escherichia coli." Biochim Biophys Acta 1425(2);377-86. PMID: 9795253
Daruwala96: Daruwala R, Kwon O, Meganathan R, Hudspeth ME (1996). "A new isochorismate synthase specifically involved in menaquinone (vitamin K2) biosynthesis encoded by the menF gene." FEMS Microbiol Lett 1996;140(2-3);159-63. PMID: 8764478
Daruwala97: Daruwala R, Bhattacharyya DK, Kwon O, Meganathan R (1997). "Menaquinone (vitamin K2) biosynthesis: overexpression, purification, and characterization of a new isochorismate synthase from Escherichia coli." J Bacteriol 1997;179(10);3133-8. PMID: 9150206
Fang11: Fang M, Macova A, Hanson KL, Kos J, Palmer DR (2011). "Using substrate analogues to probe the kinetic mechanism and active site of Escherichia coli MenD." Biochemistry 50(40);8712-21. PMID: 21928762
Gross06b: Gross J, Cho WK, Lezhneva L, Falk J, Krupinska K, Shinozaki K, Seki M, Herrmann RG, Meurer J (2006). "A plant locus essential for phylloquinone (vitamin K1) biosynthesis originated from a fusion of four eubacterial genes." J Biol Chem 281(25);17189-96. PMID: 16617180
Heide81: Heide L, Leistner E (1981). "Enzymatic synthesis of the coenzyme A ester of o-succinylbenzoic acid, an intermediate in menaquinone (vitamin K2) biosynthesis." FEBS Lett 128(2);201-4. PMID: 7262311
Heide82: Heide L, Arendt S, Leistner E (1982). "Enzymatic synthesis, characterization, and metabolism of the coenzyme A ester of o-succinylbenzoic acid, an intermediate in menaquinone (vitamin K2) biosynthesis." J Biol Chem 1982;257(13);7396-400. PMID: 7045104
Huycke01: Huycke MM, Moore D, Joyce W, Wise P, Shepard L, Kotake Y, Gilmore MS (2001). "Extracellular superoxide production by Enterococcus faecalis requires demethylmenaquinone and is attenuated by functional terminal quinol oxidases." Mol Microbiol 42(3);729-40. PMID: 11722738
Jiang07: Jiang M, Cao Y, Guo ZF, Chen M, Chen X, Guo Z (2007). "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." Biochemistry 46(38);10979-89. PMID: 17760421
Jiang08: Jiang M, Chen X, Guo ZF, Cao Y, Chen M, Guo Z (2008). "Identification and Characterization of (1R,6R)-2-Succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate Synthase in the Menaquinone Biosynthesis of Escherichia coli." Biochemistry 47(11);3426-34. PMID: 18284213
Jiang10: Jiang M, Chen M, Guo ZF, Guo Z (2010). "A bicarbonate cofactor modulates 1,4-dihydroxy-2-naphthoyl-coenzyme a synthase in menaquinone biosynthesis of Escherichia coli." J Biol Chem 285(39);30159-69. PMID: 20643650
Johnson00: Johnson TW, Shen G, Zybailov B, Kolling D, Reategui R, Beauparlant S, Vassiliev IR, Bryant DA, Jones AD, Golbeck JH, Chitnis PR (2000). "Recruitment of a foreign quinone into the A(1) site of photosystem I. I. Genetic and physiological characterization of phylloquinone biosynthetic pathway mutants in Synechocystis sp. pcc 6803." J Biol Chem 275(12);8523-30. PMID: 10722690
Kerbarh05: Kerbarh O, Ciulli A, Howard NI, Abell C (2005). "Salicylate biosynthesis: overexpression, purification, and characterization of Irp9, a bifunctional salicylate synthase from Yersinia enterocolitica." J Bacteriol 187(15);5061-6. PMID: 16030197
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