Escherichia coli K-12 substr. MG1655 Enzyme: phosphoglucose isomerase

Gene: pgi Accession Numbers: EG10702 (EcoCyc), b4025, ECK4017

Regulation Summary Diagram: ?

Regulation summary diagram for pgi

Subunit composition of phosphoglucose isomerase = [Pgi]2

Phosphoglucose isomerase catalyzes the interconversion of glucose-6-phosphate and fructose-6-phosphate, an essential step of the glycolysis and gluconeogenesis pathways.

The enzyme is dimeric in solution, but an additional higher molecular weight form that is less active and more negatively charged was found as well [Schreyer80].

A pgi mutant grows slowly on glucose and utilizes glucose primarily via the pentose phosphate pathway as the source of NADPH [Fraenkel67, Csonka77, Canonaco01, Hua03]; the Entner-Doudoroff pathway I is also used to a lesser degree [Loomis66]. The glyoxylate shunt is also active in a pgi mutant strain [Hua03]. The increased flux through the pentose phosphate pathway leads to overproduction of NADPH and thus disturbs the redox balance [Kabir03a, Kabir03], which may be restored by overexpressing SthA [Canonaco01] or a heterologous NADPH-utilizing pathway [Kabir03a, Kabir03]. Deletion of pgi is a common strategy for metabolic engineering of E. coli, e.g. [Simkhada09, Kurumbang10, Kim10b, Kim11, Ahn11].

pgi mutant strains that were allowed to evolve for 600-800 generations have been characterized [Fong06, Charusanti10]. When grown on maltose, pgi mutants accumulate maltodextrin and thus stain blue with iodine (the "maltose Blu phenotype") [Roehl79]. pgi expression is induced by oxidative stress, and a pgi deletion mutant is hypersensitive to oxidative stress induced by paraquat [Rungrassamee08]. pgi insertion mutants were identified in a genetic screen for genes that are important for survival of exposure to ionizing radiation (IR). A pgi deletion mutant has a moderate decrease in IR survival [Byrne14].

Phosphoglucose isomerase activity is positively regulated by CsrA [Sabnis95].

pgi is one of a network of genes believed to play a role in promoting the stress-induced mutagenesis (SIM) response of E. coli K-12 [Al12].

Pgi: "phosphoglucose isomerase" [Fraenkel67]

Citations: [Fraenkel67a]

Locations: periplasmic space, cytosol

Map Position: [4,231,781 -> 4,233,430] (91.21 centisomes, 328°)
Length: 1650 bp / 549 aa

Molecular Weight of Polypeptide: 61.53 kD (from nucleotide sequence), 59.0 kD (experimental) [Schreyer80 ]

Molecular Weight of Multimer: 125.0 kD (experimental) [Schreyer80]

Unification Links: ASAP:ABE-0013163 , CGSC:409 , DIP:DIP-35887N , EchoBASE:EB0696 , EcoGene:EG10702 , EcoliWiki:b4025 , ModBase:P0A6T1 , OU-Microarray:b4025 , PortEco:pgi , PR:PRO_000025181 , Pride:P0A6T1 , Protein Model Portal:P0A6T1 , RefSeq:NP_418449 , RegulonDB:EG10702 , SMR:P0A6T1 , String:511145.b4025 , Swiss-Model:P0A6T1 , UniProt:P0A6T1

Relationship Links: InterPro:IN-FAMILY:IPR001672 , InterPro:IN-FAMILY:IPR018189 , InterPro:IN-FAMILY:IPR023096 , Panther:IN-FAMILY:PTHR11469 , PDB:Structure:3NBU , Pfam:IN-FAMILY:PF00342 , Prints:IN-FAMILY:PR00662 , Prosite:IN-FAMILY:PS00174 , Prosite:IN-FAMILY:PS00765 , Prosite:IN-FAMILY:PS51463

In Paralogous Gene Group: 486 (2 members)

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for pgi

GO Terms:

Biological Process: GO:0006096 - glycolytic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, UniProtGOA11, GOA06, GOA01, Fraenkel67]
GO:0034599 - cellular response to oxidative stress Inferred from experiment [Rungrassamee08]
GO:0006094 - gluconeogenesis Inferred by computational analysis [UniProtGOA11, GOA06, GOA01]
Molecular Function: GO:0004347 - glucose-6-phosphate isomerase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Schreyer80, Loomis66, Ishii07]
GO:0042802 - identical protein binding Inferred from experiment [Rajagopala14, Lasserre06]
GO:0042803 - protein homodimerization activity Inferred from experiment [Schreyer80]
GO:0016853 - isomerase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, Lasserre06]
GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, GOA06]
GO:0030288 - outer membrane-bounded periplasmic space [Friedberg72]

MultiFun Terms: metabolism central intermediary metabolism
metabolism energy metabolism, carbon glycolysis

Essentiality data for pgi knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Created 14-Jun-2010 by Keseler I , SRI International
Last-Curated ? 15-Jun-2010 by Keseler I , SRI International

Enzymatic reaction of: phosphoglucose isomerase

Synonyms: glucose-6-phosphate isomerase, D-glucose-6-phosphate-ketol-isomerase

EC Number:

β-D-glucose 6-phosphate <=> β-D-fructofuranose 6-phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

This reaction is reversible. [Ishii07]

In Pathways: colanic acid building blocks biosynthesis , O-antigen building blocks biosynthesis (E. coli) , superpathway of glycolysis and Entner-Doudoroff , superpathway of glycolysis, pyruvate dehydrogenase, TCA, and glyoxylate bypass , GDP-mannose biosynthesis , gluconeogenesis I , UDP-N-acetyl-D-glucosamine biosynthesis I , glycolysis I (from glucose 6-phosphate)

The equilibrium constant for the reaction is 0.30 [Ishii07].

Citations: [KLUNGSOEYR64]

Inhibitors (Competitive): phosphoenolpyruvate [Ogawa07a]

Inhibitors (Unknown Mechanism): D-gluconate 6-phosphate [Schreyer80]

Kinetic Parameters:

Km (μM)
β-D-fructofuranose 6-phosphate
[Schreyer80, BRENDA14]
β-D-fructofuranose 6-phosphate
β-D-glucose 6-phosphate

pH(opt): 8 [Schreyer80]

Sequence Features

Protein sequence of Pgi with features indicated

Feature Class Location Citations Comment
N6-acetyllysine-Modification 80
[Zhang09, UniProt15]
UniProt: N6-acetyllysine.
N6-acetyllysine-Modification 228
[Zhang09, UniProt15]
UniProt: N6-acetyllysine.
N6-acetyllysine-Modification 234
[Zhang09, UniProt15]
UniProt: N6-acetyllysine.
Sequence-Conflict 317
[Smith92a, Froman89, UniProt10a]
UniProt: (in Ref. 1 and 2);
Active-Site 355
UniProt: Proton donor; Non-Experimental Qualifier: by similarity;
Active-Site 386
UniProt: Non-Experimental Qualifier: by similarity;
Acetylation-Modification 449
Active-Site 514
UniProt: Non-Experimental Qualifier: by similarity;

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


10/20/97 Gene b4025 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10702; confirmed by SwissProt match.


Ahn11: Ahn J, Chung BK, Lee DY, Park M, Karimi IA, Jung JK, Lee H (2011). "NADPH-dependent pgi-gene knockout Escherichia coli metabolism producing shikimate on different carbon sources." FEMS Microbiol Lett 324(1);10-6. PMID: 22092758

Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554

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

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

Byrne14: Byrne RT, Chen SH, Wood EA, Cabot EL, Cox MM (2014). "Escherichia coli genes and pathways involved in surviving extreme exposure to ionizing radiation." J Bacteriol 196(20);3534-45. PMID: 25049088

Canonaco01: Canonaco F, Hess TA, Heri S, Wang T, Szyperski T, Sauer U (2001). "Metabolic flux response to phosphoglucose isomerase knock-out in Escherichia coli and impact of overexpression of the soluble transhydrogenase UdhA." FEMS Microbiol Lett 204(2);247-52. PMID: 11731130

Charusanti10: Charusanti P, Conrad TM, Knight EM, Venkataraman K, Fong NL, Xie B, Gao Y, Palsson BO (2010). "Genetic basis of growth adaptation of Escherichia coli after deletion of pgi, a major metabolic gene." PLoS Genet 6(11);e1001186. PMID: 21079674

Csonka77: Csonka LN, Fraenkel DG (1977). "Pathways of NADPH formation in Escherichia coli." J Biol Chem 252(10);3382-91. PMID: 16899

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

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Fong06: Fong SS, Nanchen A, Palsson BO, Sauer U (2006). "Latent pathway activation and increased pathway capacity enable Escherichia coli adaptation to loss of key metabolic enzymes." J Biol Chem 281(12);8024-33. PMID: 16319065

Fraenkel67: Fraenkel DG, Levisohn SR (1967). "Glucose and gluconate metabolism in an Escherichia coli mutant lacking phosphoglucose isomerase." J Bacteriol 93(5);1571-8. PMID: 5337843

Fraenkel67a: Fraenkel DG (1967). "Genetic mapping of mutations affecting phosphoglucose isomerase and fructose diphosphatase in Escherichia coli." J Bacteriol 93(5);1582-7. PMID: 4290578

Friedberg72: Friedberg I (1972). "Localization of phosphoglucose isomerase in Escherichia coli and its relation to the induction of the hexose phosphate transport system." J Bacteriol 1972;112(3);1201-5. PMID: 4344919

Froman89: Froman BE, Tait RC, Gottlieb LD (1989). "Isolation and characterization of the phosphoglucose isomerase gene from Escherichia coli." Mol Gen Genet 1989;217(1);126-31. PMID: 2549364

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

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

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

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

Hua03: Hua Q, Yang C, Baba T, Mori H, Shimizu K (2003). "Responses of the central metabolism in Escherichia coli to phosphoglucose isomerase and glucose-6-phosphate dehydrogenase knockouts." J Bacteriol 185(24);7053-67. PMID: 14645264

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

Ishii07: Ishii N, Suga Y, Hagiya A, Watanabe H, Mori H, Yoshino M, Tomita M (2007). "Dynamic simulation of an in vitro multi-enzyme system." FEBS Lett 581(3);413-20. PMID: 17239859

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kabir03: Kabir MM, Shimizu K (2003). "Gene expression patterns for metabolic pathway in pgi knockout Escherichia coli with and without phb genes based on RT-PCR." J Biotechnol 105(1-2);11-31. PMID: 14511906

Kabir03a: Kabir MM, Shimizu K (2003). "Fermentation characteristics and protein expression patterns in a recombinant Escherichia coli mutant lacking phosphoglucose isomerase for poly(3-hydroxybutyrate) production." Appl Microbiol Biotechnol 62(2-3);244-55. PMID: 12883871

Kim10b: Kim J, Reed JL (2010). "OptORF: Optimal metabolic and regulatory perturbations for metabolic engineering of microbial strains." BMC Syst Biol 4(1);53. PMID: 20426856

Kim11: Kim S, Lee CH, Nam SW, Kim P (2011). "Alteration of reducing powers in an isogenic phosphoglucose isomerase (pgi)-disrupted Escherichia coli expressing NAD(P)-dependent malic enzymes and NADP-dependent glyceraldehyde 3-phosphate dehydrogenase." Lett Appl Microbiol 52(5);433-40. PMID: 21272045

KLUNGSOEYR64: Klungsoyr L, Endresen A "Intracellular pH effect upon phosphoglucose isomerase in Escherichia coli." Biochim Biophys Acta 1964;92:378-387. PMID: 14249126

Kurumbang10: Kurumbang NP, Liou K, Sohng JK (2010). "Biosynthesis of paromamine derivatives in engineered Escherichia coli by heterologous expression." J Appl Microbiol 108(5);1780-8. PMID: 19895652

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

Loomis66: Loomis WF, Magasanik B (1966). "Nature of the effector of catabolite repression of beta-galactosidase in Escherichia coli." J Bacteriol 92(1);170-7. PMID: 5328748

Ogawa07a: Ogawa T, Mori H, Tomita M, Yoshino M (2007). "Inhibitory effect of phosphoenolpyruvate on glycolytic enzymes in Escherichia coli." Res Microbiol 158(2);159-63. PMID: 17307338

Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554

Roehl79: Roehl RA, Vinopal RT (1979). "New maltose Blu mutations in Escherichia coli K-12." J Bacteriol 139(2);683-5. PMID: 88439

Rungrassamee08: Rungrassamee W, Liu X, Pomposiello PJ (2008). "Activation of glucose transport under oxidative stress in Escherichia coli." Arch Microbiol 190(1):41-9. PMID: 18368388

Sabnis95: Sabnis NA, Yang H, Romeo T (1995). "Pleiotropic regulation of central carbohydrate metabolism in Escherichia coli via the gene csrA." J Biol Chem 1995;270(49);29096-104. PMID: 7493933

Schreyer80: Schreyer R, Bock A (1980). "Phosphoglucose isomerase from Escherischia coli K 10: purification, properties and formation under aerobic and anaerobic condition." Arch Microbiol 127(3);289-98. PMID: 7004378

Simkhada09: Simkhada D, Kim E, Lee HC, Sohng JK (2009). "Metabolic engineering of Escherichia coli for the biological synthesis of 7-O-xylosyl naringenin." Mol Cells 28(4);397-401. PMID: 19812897

Smith92a: Smith MW, Doolittle RF (1992). "Anomalous phylogeny involving the enzyme glucose-6-phosphate isomerase." J Mol Evol 34(6);544-5. PMID: 1593646

Thomson79: Thomson J, Gerstenberger PD, Goldberg DE, Gociar E, Orozco de Silva A, Fraenkel DG (1979). "ColE1 hybrid plasmids for Escherichia coli genes of glycolysis and the hexose monophosphate shunt." J Bacteriol 1979;137(1);502-6. PMID: 368027

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

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."

Vinopal75: Vinopal RT, Hillman JD, Schulman H, Reznikoff WS, Fraenkel DG (1975). "New phosphoglucose isomerase mutants of Escherichia coli." J Bacteriol 122(3);1172-4. PMID: 1097391

Yu08: Yu BJ, Kim JA, Moon JH, Ryu SE, Pan JG (2008). "The diversity of lysine-acetylated proteins in Escherichia coli." J Microbiol Biotechnol 18(9);1529-36. PMID: 18852508

Zhang09: Zhang J, Sprung R, Pei J, Tan X, Kim S, Zhu H, Liu CF, Grishin NV, Zhao Y (2009). "Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli." Mol Cell Proteomics 8(2);215-25. PMID: 18723842

Other References Related to Gene Regulation

Martin02: Martin RG, Rosner JL (2002). "Genomics of the marA/soxS/rob regulon of Escherichia coli: identification of directly activated promoters by application of molecular genetics and informatics to microarray data." Mol Microbiol 44(6);1611-24. PMID: 12067348

Olvera09: Olvera L, Mendoza-Vargas A, Flores N, Olvera M, Sigala JC, Gosset G, Morett E, Bolivar F (2009). "Transcription analysis of central metabolism genes in Escherichia coli. Possible roles of sigma38 in their expression, as a response to carbon limitation." PLoS One 4(10);e7466. PMID: 19838295

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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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