Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store

Escherichia coli K-12 substr. MG1655 Pathway: preQ0 biosynthesis
Inferred from experiment

Pathway diagram: preQ0 biosynthesis

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

Genetic Regulation Schematic

Genetic regulation schematic for preQ0 biosynthesis

Synonyms: deazapurine biosynthesis

Superclasses: BiosynthesisSecondary Metabolites Biosynthesis

7-Deazapurines are compounds that contain pyrrolopyrimidine functional groups (similar to purines, but lackinging one of the nitrogens in the pentameric ring). These compounds form a structurally diverse class of nucleoside analogues that often possess antibiotic, antineoplastic, or antiviral activities.

An important 7-deazapurine compound is queuosine, a modified nucleoside that is present in certain tRNAs in bacteria and most eukaryotes (with the exception of mycoplasmas and yeast), but not in the archaea [IwataReuyl03]. The pathway describing the biosynthesis of queuosine can be found at queuosine biosynthesis.

The biosynthesis of all 7-deazapurines proceeds via the common intermediate preQ0, which is produced in four steps from the nucleotide GTP. The pathway starts with the conversion of GTP to 7,8-dihydroneopterin 3'-triphosphate by GTP cyclohydrolase I, an enzyme that is also involved in the biosynthesis of tetrahydropteroyl mono-L-glutamate. 7,8-dihydroneopterin 3'-triphosphate is converted to 6-carboxy-5,6,7,8-tetrahydropterin by the action of 6-carboxy-5,6,7,8-tetrahydropterin synthase.

This intermediate is converted to 7-carboxy-7-deazaguanine by an unusual transformation catalyzed by 7-carboxy-7-deazaguanine synthase ( queE), a member of the radical SAM enzyme superfamily. The corresponding E. coli enzyme has not yet been identified, but an ortholog, queE, exists.

Finally, the carboxylate moiety of 7-carboxy-7-deazaguanine is converted to a nitrile in an ATP-dependent reaction in which ammonia serves as the nitrogen source. The reaction is catalyzed by 7-cyano-7-deazaguanine synthase, generating the final product, preQ0 [McCarty09].

Last-Curated 26-Apr-2011 by Keseler I, SRI International


IwataReuyl03: Iwata-Reuyl D (2003). "Biosynthesis of the 7-deazaguanosine hypermodified nucleosides of transfer RNA." Bioorg Chem 31(1);24-43. PMID: 12697167

McCarty08: McCarty RM, Bandarian V (2008). "Deciphering deazapurine biosynthesis: pathway for pyrrolopyrimidine nucleosides toyocamycin and sangivamycin." Chem Biol 15(8);790-8. PMID: 18721750

McCarty09: McCarty RM, Somogyi A, Lin G, Jacobsen NE, Bandarian V (2009). "The deazapurine biosynthetic pathway revealed: in vitro enzymatic synthesis of PreQ(0) from guanosine 5'-triphosphate in four steps." Biochemistry 48(18);3847-52. PMID: 19354300

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

Auerbach00: Auerbach G, Herrmann A, Bracher A, Bader G, Gutlich M, Fischer M, Neukamm M, Garrido-Franco M, Richardson J, Nar H, Huber R, Bacher A (2000). "Zinc plays a key role in human and bacterial GTP cyclohydrolase I." Proc Natl Acad Sci U S A 97(25);13567-72. PMID: 11087827

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Burg68: Burg AW, Brown GM (1968). "The biosynthesis of folic acid. 8. Purification and properties of the enzyme that catalyzes the production of formate from carbon atom 8 of guanosine triphosphate." J Biol Chem 1968;243(9);2349-58. PMID: 4296838

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

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

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

Gaur05: Gaur R, Varshney U (2005). "Genetic analysis identifies a function for the queC (ybaX) gene product at an initial step in the queuosine biosynthetic pathway in Escherichia coli." J Bacteriol 187(20);6893-901. PMID: 16199558

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: 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."

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Katzenmeier91: Katzenmeier G, Schmid C, Kellermann J, Lottspeich F, Bacher A (1991). "Biosynthesis of tetrahydrofolate. Sequence of GTP cyclohydrolase I from Escherichia coli." Biol Chem Hoppe Seyler 1991;372(11);991-7. PMID: 1665332

Lee02: Lee S, Ahn C, Park E, Hwang DS, Yim J (2002). "Biochemical characterization of oligomerization of Escherichia coli GTP cyclohydrolase I." J Biochem Mol Biol 35(3);255-61. PMID: 12297008

Leichert04: Leichert LI, Jakob U (2004). "Protein thiol modifications visualized in vivo." PLoS Biol 2(11);e333. PMID: 15502869

Marincs06: Marincs F, Manfield IW, Stead JA, McDowall KJ, Stockley PG (2006). "Transcript analysis reveals an extended regulon and the importance of protein-protein co-operativity for the Escherichia coli methionine repressor." Biochem J 396(2);227-34. PMID: 16515535

McCarty09a: McCarty RM, Somogyi A, Bandarian V (2009). "Escherichia coli QueD Is a 6-Carboxy-5,6,7,8-tetrahydropterin Synthase (dagger)." Biochemistry 48(11);2301-3. PMID: 19231875

Meining95: Meining W, Bacher A, Bachmann L, Schmid C, Weinkauf S, Huber R, Nar H (1995). "Elucidation of crystal packing by X-ray diffraction and freeze-etching electron microscopy. Studies on GTP cyclohydrolase I of Escherichia coli." J Mol Biol 253(1);208-18. PMID: 7473713

Miles14: Miles ZD, Roberts SA, McCarty RM, Bandarian V (2014). "Biochemical and structural studies of 6-carboxy-5,6,7,8-tetrahydropterin synthase reveal the molecular basis of catalytic promiscuity within the tunnel-fold superfamily." J Biol Chem 289(34);23641-52. PMID: 24990950

Nar95: Nar H, Huber R, Meining W, Schmid C, Weinkauf S, Bacher A (1995). "Atomic structure of GTP cyclohydrolase I." Structure 3(5);459-66. PMID: 7663943

Nar95a: Nar H, Huber R, Auerbach G, Fischer M, Hosl C, Ritz H, Bracher A, Meining W, Eberhardt S, Bacher A (1995). "Active site topology and reaction mechanism of GTP cyclohydrolase I." Proc Natl Acad Sci U S A 92(26);12120-5. PMID: 8618856

Showing only 20 references. To show more, press the button "Show all references".

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by Pathway Tools version 19.5 (software by SRI International) on Tue May 3, 2016, biocyc14.