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Escherichia coli K-12 substr. MG1655 Pathway: superpathway of menaquinol-8 biosynthesis I

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

Synonyms: vitamin K2 biosynthesis I, superpathway of menaquinone-8 biosynthesis I

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Quinol and Quinone Biosynthesis Menaquinol Biosynthesis
Superpathways

Pathway Summary from MetaCyc:
General Background

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].

Menaquinones are known to have side chains of different sizes in different organisms, and sometimes even within the same organism. The most common menaquinones contain 7, 8 and 9 isoprene units. However, menaquinones containing 4 [Hollander77, Cawthorne67], 5 [Cawthorne67, Dunphy71], 6 [Dunphy71, Shah80, Weber70, Maroc70], 10 [Shah80, Collins80], 11 [Shah80, Collins80], 12 [Shah80], and 13 [Shah80] isoprene units have been reported in bacteria.

About This Pathway

The best characterized menaquinone biosynthetic pathway is that of Escherichia coli K-12 that synthesizes menaquinone-8 (MK-8). MK-8 is not unique to E. coli, and is found in many different bacterial species.

A study of the quinones of halophilic archaebacteria found that MK-8 was the major quinone in most species included in the study, including Haloferax volcanii, Halococcus morrhuae, Halobacterium salinarum, Halorubrum saccharovorum and Halorubrum trapanicum [Mullakhanbhai72, Kushwaha74, Collins81a].

MK-8 is very common in facultatively anaerobic Gram negative bacteria, such as the enterobacteria. In addition to Escherichia coli K-12 it has been documented in Citrobacter freundii, Enterobacter aerogenes, Pectobacterium carotovorum, Proteus mirabilis, Proteus vulgaris [Whistance69] and Serratia marcescens [Bezborodov69], as well as the non-eneterobacteria Aeromonas hydrophila, Aeromonas caviae [Whistance69] and Salinivibrio costicola [Collins81a]. MK-8 has not been discovered in obligate anaerobes so far

Some aerobic Gram-negative bacteria that contain MK-8 as their major quinone include the gliding bacterium Myxococcus fulvus [Kleinig74], and several members of the Deinococcus-Thermus phylum, including Thermus aquaticus and Thermus thermophilus [Collins80, Collins81], Deinococcus radiophilus and Deinococcus radiodurans [Yamada77].

Even though most Gram-positive bacteria contain menaquinone-7 as their major quinone, a few are known to make MK-8 instead, including Virgibacillus pantothenticus [Hess79], Bacillus thuringiensis [Hess79], Lactobacillus mali [Collins80], Nesterenkonia halobia [Collins81a], certain Micrococcus luteus strains [Watanuki72, Yamada76], and Planococcus citreus [Yamada76].

MK-8 was also found as a minor component in the phototrophic bacteria Allochromatium vinosum [Osnitskaya64], Rubrivivax gelatinosus and Rhodospirillum sp. 2761 [Maroc68].

Subpathways: demethylmenaquinol-8 biosynthesis I , menaquinol-8 biosynthesis , 1,4-dihydroxy-2-naphthoate biosynthesis I , octaprenyl diphosphate biosynthesis

Credits:
Created 31-Jan-1995 by Riley M , Marine Biological Laboratory
Revised 03-Apr-2007 by Keseler I , SRI International
Revised 05-Mar-2008 by Caspi R , SRI International


References

Bezborodov69: Bezborodov, A. M., Chermenskaya, T.S. (1969). "Biosynthesis of 8-ubiquinone and vitamin K2(40) by Serratia marcescens strain 42." Prikl. Biokhim. Mikrobiol. 5:620-623.

Cawthorne67: Cawthorne MA, Jeffries LR, Harris M, Price SA, Diplock AT, Green J (1967). "Menaquinone-4 and -5 in a bacterium." Biochem J 104(2);35contd-36c. PMID: 6048777

Collins80: Collins MD, Shah HN, Minnikin DE (1980). "A note on the separation of natural mixtures of bacterial menaquinones using reverse phase thin-layer chromatography." J Appl Bacteriol 48(2);277-82. PMID: 7462123

Collins81: Collins MD, Jones D (1981). "Distribution of isoprenoid quinone structural types in bacteria and their taxonomic implication." Microbiol Rev 45(2);316-54. PMID: 7022156

Collins81a: Collins, M.D., Ross, H. N. M., Tindall, B. J., Grant, W. D. (1981). "Distribution of isoprenoid quinones in halophilic bacteria." J. Appl. Bacteriol. 50:559-565.

Dam35: Dam, H. (1935). "The antihaemorrhagic vitamin of the chick: occurrence and chemical nature." Nature 135:652-653.

Doisy40: Doisy EA, Binkley SB, Thayer SA, McKee RW (1940). "Vitamin K." Science 91(2351);58-62. PMID: 17783315

Dunphy71: Dunphy PJ, Phillips PG, Brodie AF (1971). "Separation and identification of menaquinones from microorganisms." J Lipid Res 12(4);442-9. PMID: 5005959

Farrand73: Farrand SK, Taber HW (1973). "Physiological effects of menaquinone deficiency in Bacillus subtilis." J Bacteriol 115(3);1035-44. PMID: 4353869

Farrand74: Farrand SK, Taber HW (1974). "Changes in menaquinone concentration during growth and early sporulation in Bacillus subtilis." J Bacteriol 117(1);324-6. PMID: 4202999

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

Hess79: Hess A, Hollander R, Mannheim W (1979). "Lipoquinones of some spore-forming rods, lactic-acid bacteria and actinomycetes." J Gen Microbiol 115(1);247-52. PMID: 119033

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

Hollander76: Hollander R (1976). "Correlation of the function of demethylmenaquinone in bacterial electron transport with its redox potential." FEBS Lett 72(1);98-100. PMID: 187454

Hollander77: Hollander R, Wolf G, Mannheim W (1977). "Lipoquinones of some bacteria and mycoplasmas, with considerations on their functional significance." Antonie Van Leeuwenhoek 43(2);177-85. PMID: 413478

Isler58: Isler, O, Ruegg, R., Chopard-dit-Jean, L. H., Winterstein, A., Wiss, O. (1958). "Synthese und Isolierung von Vitamin K und Isoprenologen Verbindungen." Helv. Chim. Acta 41:786-807.

Kleinig74: Kleinig H, Reichenbach H, Theobald N, Achenbach H (1974). "Flexibacter elegans and Myxococcus fulvus: aerobic Gram-negative bacteria containing menaquinones as the only isoprenoid quinones." Arch Microbiol 101(1);91-3. PMID: 4216336

Kushwaha74: Kushwaha SC, Gochnauer MB, Kushner DJ, Kates M (1974). "Pigments and isoprenoid compounds in extremely and moderately halophilic bacteria." Can J Microbiol 20(2);241-5. PMID: 4822788

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

Maroc68: Maroc J, de Klerk H, Kamen MD (1968). "Quinones of Athiorhodaceae." Biochim Biophys Acta 162(4);621-3. PMID: 5727384

Maroc70: Maroc J, Azerad R, Kamen MD, Le Gall J (1970). "Menaquinone (MK-6) in the sulfate-reducing obligate anaerobe, Desulfovibrio." Biochim Biophys Acta 197(1);87-9. PMID: 5412037

Meganathan01a: Meganathan R (2001). "Biosynthesis of menaquinone (vitamin K2) and ubiquinone (coenzyme Q): a perspective on enzymatic mechanisms." Vitam Horm 61;173-218. PMID: 11153266

Mullakhanbhai72: Mullakhanbhai MF, Francis GW (1972). "Bacterial lipids. 1. Lipid constituents of a moderately halophilic bacterium." Acta Chem Scand 26(4);1399-410. PMID: 5049648

Osnitskaya64: Osnitskaya, L.K., Threlfall, D.R., Goodwin, T.W. (1964). "Ubiquinone-40 and vitamin K-2 (40) in Chromatium vinosum." Nature 204;80-1. PMID: 14240125

Shah80: Shah HN, Collins MD (1980). "Fatty acid and isoprenoid quinone composition in the classification of Bacteroides melaninogenicus and related taxa." J Appl Bacteriol 48(1);75-87. PMID: 6102980

Watanuki72: Watanuki, M., Aida, K. (1972). "Significance of quinones in the clasification of bacteria." J. Gen. Appl. Microbiol. 18:469-472.

Weber70: Weber MM, Matschiner JT, Peck HD (1970). "Menaquinone-6 in the strict anaerobes Desulfovibrio vulgaris and Desulfovibrio gigas." Biochem Biophys Res Commun 38(2);197-204. PMID: 5418698

Whistance69: Whistance GR, Dillon JF, Threlfall DR (1969). "The nature, intergeneric distribution and biosynthesis of isoprenoid quinones and phenols in gram-negative bacteria." Biochem J 111(4);461-72. PMID: 4886765

Yamada76: Yamada, Y., Inouye, G., Tahara, Y., Kondo, K. (1976). "The menaquinone system in the classification of aerobic gram-positive cocci in the genera Micrococcus, Staphylococcus, Planococcus and Sporosarcina." J. Gen. Appl. Microbiol. 22:227-236.

Yamada77: Yamada, Y., Takinami, H., Tahara, Y., Kondo, K. (1977). "The menaquinone system in the classification of radiation-resistant micrococci." J. Gen. AppL MicrobioL 23:105-108.

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Asai94: Asai K, Fujisaki S, Nishimura Y, Nishino T, Okada K, Nakagawa T, Kawamukai M, Matsuda H (1994). "The identification of Escherichia coli ispB (cel) gene encoding the octaprenyl diphosphate synthase." Biochem Biophys Res Commun 202(1);340-5. PMID: 8037730

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Badger05: Badger J, Sauder JM, Adams JM, Antonysamy S, Bain K, Bergseid MG, Buchanan SG, Buchanan MD, Batiyenko Y, Christopher JA, Emtage S, Eroshkina A, Feil I, Furlong EB, Gajiwala KS, Gao X, He D, Hendle J, Huber A, Hoda K, Kearins P, Kissinger C, Laubert B, Lewis HA, Lin J, Loomis K, Lorimer D, Louie G, Maletic M, Marsh CD, Miller I, Molinari J, Muller-Dieckmann HJ, Newman JM, Noland BW, Pagarigan B, Park F, Peat TS, Post KW, Radojicic S, Ramos A, Romero R, Rutter ME, Sanderson WE, Schwinn KD, Tresser J, Winhoven J, Wright TA, Wu L, Xu J, Harris TJ (2005). "Structural analysis of a set of proteins resulting from a bacterial genomics project." Proteins 60(4);787-96. PMID: 16021622

Baisa13: Baisa G, Stabo NJ, Welch RA (2013). "Characterization of Escherichia coli D-Cycloserine Transport and Resistant Mutants." J Bacteriol 195(7);1389-99. PMID: 23316042

Bentley82: Bentley R, Meganathan R (1982). "Biosynthesis of vitamin K (menaquinone) in bacteria." Microbiol Rev 46(3);241-80. PMID: 6127606

Bentley83: Bentley R, Meganathan R (1983). "Vitamin K biosynthesis in bacteria--precursors, intermediates, enzymes, and genes." J Nat Prod 46(1);44-59. PMID: 6406647

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

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Buss01: Buss K, Muller R, Dahm C, Gaitatzis N, Skrzypczak-Pietraszek E, Lohmann S, Gassen M, Leistner E (2001). "Clustering of isochorismate synthase genes menF and entC and channeling of isochorismate in Escherichia coli." Biochim Biophys Acta 1522(3);151-7. PMID: 11779629

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Chang12: Chang KM, Chen SH, Kuo CJ, Chang CK, Guo RT, Yang JM, Liang PH (2012). "Roles of amino acids in the Escherichia coli octaprenyl diphosphate synthase active site probed by structure-guided site-directed mutagenesis." Biochemistry 51(16);3412-9. PMID: 22471615

Chen11b: 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

Chen13d: 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

Choi09a: Choi JH, Ryu YW, Park YC, Seo JH (2009). "Synergistic effects of chromosomal ispB deletion and dxs overexpression on coenzyme Q(10) production in recombinant Escherichia coli expressing Agrobacterium tumefaciens dps gene." J Biotechnol 144(1);64-9. PMID: 19409940

Cui10: Cui TZ, Kaino T, Kawamukai M (2010). "A subunit of decaprenyl diphosphate synthase stabilizes octaprenyl diphosphate synthase in Escherichia coli by forming a high-molecular weight complex." FEBS Lett 584(4);652-6. PMID: 20051244

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

Daley05: Daley DO, Rapp M, Granseth E, Melen K, Drew D, von Heijne G (2005). "Global topology analysis of the Escherichia coli inner membrane proteome." Science 308(5726);1321-3. PMID: 15919996

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

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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