This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: demethylmenaquinone-8 biosynthesis II
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Quinol and Quinone Biosynthesis → Demethylmenaquinol Biosynthesis → Demethylmenaquinol-8 Biosynthesis|
Some taxa known to possess this pathway include : Chlamydia muridarum , Chlamydia trachomatis , Chlamydophila abortus , Chlamydophila caviae , Chlamydophila felis , Leptospira borgpetersenii , Leptospira interrogans , Streptomyces coelicolor , Streptomyces coelicolor A3(2) , Thermus thermophilus , Thermus thermophilus HB8
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 [Meganathan01]. 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, Li11a, 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
Most bacteria appear to synthesize menaquinone from chorismate by seven enzymes in a well characterized route (see superpathway of menaquinol-8 biosynthesis I). Recently an alternative pathway for the biosynthesis of menaquinone from chorismate has been identified in some bacteria, including Streptomyces coelicolor and Thermus thermophilus [Hiratsuka08]. Initial analysis of sequenced genomes suggested that the pathway may be present in a variety of organisms, including the bacterial pathogens Campylobacter jejuni and Helicobacter pylori, and members of the genera Deltaproteobacteria, Epsilonproteobacteria, Firmicutes, Acidobacteria
The pathway, which branches at chorismate, follows a different route, including the intermediate futalosine, an unusual nucleoside derivative consisting of inosine and o-substituted benzoate moieties. Several genes that encode enzymes in this pathway have been identified by mutagenesis [Hiratsuka08], and the enzymes responsible for the steps leading from chorismate to 1,4-dihydroxy-6-naphthoate are known, although so far only one of them, futalosine hydrolase, has been characterized [Hiratsuka09]. Several genes of Streptomyces coelicolor have been implicated in the steps of the later part of the pathway, leading from 1,4-dihydroxy-6-naphthoate to demethylmenaquinone-8. Even though their roles have not been verified yet, their sequence suggests prenylation, decarboxylation and methylation, similar to the conventional pathway [Dairi09].
Superpathways: superpathway of menaquinol-8 biosynthesis II
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
Dairi09: Dairi T (2009). "An alternative menaquinone biosynthetic pathway operating in microorganisms: an attractive target for drug discovery to pathogenic Helicobacter and Chlamydia strains." J Antibiot (Tokyo) 62(7);347-52. PMID: 19557031
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
Hiratsuka09: Hiratsuka T, Itoh N, Seto H, Dairi T (2009). "Enzymatic properties of futalosine hydrolase, an enzyme essential to a newly identified menaquinone biosynthetic pathway." Biosci Biotechnol Biochem 73(5);1137-41. PMID: 19420717
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
Li11a: 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
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