Escherichia coli K-12 substr. MG1655 Pathway: demethylmenaquinol-8 biosynthesis I

Pathway diagram: demethylmenaquinol-8 biosynthesis I

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

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Synonyms: demethylmenaquinone-8 biosynthesis I

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Quinol and Quinone Biosynthesis Demethylmenaquinol Biosynthesis Demethylmenaquinol-8 Biosynthesis

General Background

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 [ECOSAL].

Superpathways: superpathway of chorismate metabolism , superpathway of menaquinol-8 biosynthesis I

Created 17-Mar-2008 by Caspi R , SRI International
Last-Curated ? 31-Jul-2014 by Keseler I , SRI International


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

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

ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Huang14: Huang H, Levin EJ, Liu S, Bai Y, Lockless SW, Zhou M (2014). "Structure of a Membrane-Embedded Prenyltransferase Homologous to UBIAD1." PLoS Biol 12(7);e1001911. PMID: 25051182

Meganathan01: Meganathan R (2001). "Biosynthesis of menaquinone (vitamin K2) and ubiquinone (coenzyme Q): a perspective on enzymatic mechanisms." Vitam Horm 61;173-218. PMID: 11153266

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

Young75: Young IG (1975). "Biosynthesis of bacterial menaquinones. Menaquinone mutants of Escherichia coli." Biochemistry 14(2);399-406. PMID: 1091286

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

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

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

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

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

Shapira07: Shapira R, Mimran E (2007). "Isolation and characterization of Escherichia coli mutants exhibiting altered response to thymol." Microb Drug Resist 13(3);157-65. PMID: 17949301

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

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

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