If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
Synonyms: demethylmenaquinone-8 biosynthesis I
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Quinol and Quinone Biosynthesis → Demethylmenaquinol Biosynthesis → Demethylmenaquinol-8 Biosynthesis|
Most aerobic Gram-negative bacteria contain ubiquinone (Q) as the sole quinone, while most aerobic Gram-positive bacteria contain menaquinone (MK) and/or demethylmenaquinone (DMK) as the main quinone. However, most of the anaerobic bacteria, regardless whether they are Gram-negative or Gram-positive, contain MK or DMK as their main quinones. Some facultatively anaerobic bacteria, such as E. coli, contain Q, MK, and DMK, which they use under different growth conditions [Meganathan01].
DMKs are known to have side chains of different sizes in different organisms, and sometimes even within the same organism. The most common DMKs contain 7, 8 and 9 isoprene units. E. coli contains demethylmenaquinone-8 (DMK-8) [Bentley83]. DMK-8 is a low-molecular weight lipophilic component of the cytoplasmic membrane and functions as a reversible redox component of the electron transfer chain, mediating electron transfer between hydrogenases and cytochromes.
DMK is also an intermediate in MK formation (see superpathway of menaquinol-8 biosynthesis I) [Meganathan01]. DMK-8 is methylated at the naphthoquinone ring to MK-8 by a methyltransferase, which uses S-adenosylmethionine as the methyl donor [Collins81].
About This Pathway
The conversion of 1,4-dihydroxy-2-naphthoate (DHNA) to DMK-8 in extracts of E. coli is catalyzed by the membrane-bound 1,4-dihydroxy-2-octaprenyltransferase (MenA). The conversion of DHNA to DMK requires replacement of the carboxyl with the isoprenoid side chain. Prenylation and decarboxylation may occur in a single active site, since symmetry experiments exclude 1,4-naphthoquinone as an intermediate. Moreover, there has been no evidence for two separate reaction steps or enzymes. Based on structural and mutagenesis data, a three-stage ionization-condensation-elimination mechanism involving a carbocation intermediate has recently been proposed [Huang14].
Review: Meganathan, R. and O. Kwon (2009) "Biosynthesis of Menaquinone (Vitamin K2) and Ubiquinone (Coenzyme Q)." EcoSal 184.108.40.206 [ECOSAL].
Shineberg76: Shineberg B, Young IG (1976). "Biosynthesis of bacterial menaquinones: the membrane-associated 1,4-dihydroxy-2-naphthoate octaprenyltransferase of Escherichia coli." Biochemistry 1976;15(13);2754-8. PMID: 949474
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Kong11: Kong MK, Lee PC (2011). "Metabolic engineering of menaquinone-8 pathway of Escherichia coli as a microbial platform for vitamin K production." Biotechnol Bioeng 108(8);1997-2002. PMID: 21445887
Rapp04: Rapp M, Drew D, Daley DO, Nilsson J, Carvalho T, Melen K, De Gier JW, Von Heijne G (2004). "Experimentally based topology models for E. coli inner membrane proteins." Protein Sci 13(4);937-45. PMID: 15044727
Suvarna98: Suvarna K, Stevenson D, Meganathan R, Hudspeth ME (1998). "Menaquinone (vitamin K2) biosynthesis: localization and characterization of the menA gene from Escherichia coli." J Bacteriol 180(10);2782-7. PMID: 9573170
Wallace77: Wallace BJ, Young IG (1977). "Role of quinones in electron transport to oxygen and nitrate in Escherichia coli. Studies with a ubiA- menA- double quinone mutant." Biochim Biophys Acta 461(1);84-100. PMID: 195602
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