Glucose oxidase

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Glucose oxidase
Structure of glucose oxidase dimer (dark and light blue) complexed with FAD (salmon) and glycans (aquamarine) from Penicillium amagasakiense.[1]
EC no.
CAS no.9001-37-0
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

The glucose oxidase enzyme (GOx or GOD) also known as notatin (EC number is an oxidoreductase that catalyses the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone. This enzyme is produced by certain species of fungi and insects and displays antibacterial activity when oxygen and glucose are present.[2]

Reaction catalyzed by glucose oxidase

Glucose oxidase is widely used for the determination of free glucose in body fluids (medical testing), in vegetal raw material, and in the food industry. It also has many applications in biotechnologies, typically enzyme assays for biochemistry including biosensors in nanotechnologies.[3][4] It was first isolated by Detlev Müller in 1928 from Aspergillus niger.[5]


Several species of fungi and insects synthesize glucose oxidase, which produces hydrogen peroxide, which kills bacteria.[2]

Notatin, extracted from antibacterial cultures of Penicillium notatum, was originally named Penicillin A, but was renamed to avoid confusion with penicillin.[6] Notatin was shown to be identical to Penicillin B and glucose oxidase, enzymes extracted from other molds besides P. notatum;[7] it is now generally known as glucose oxidase.[8]

Early experiments showed that notatin exhibits in vitro antibacterial activity (in the presence of glucose) due to hydrogen peroxide formation.[6][9] In vivo tests showed that notatin was not effective in protecting rodents from Streptococcus haemolyticus, Staphylococcus aureus, or salmonella, and caused severe tissue damage at some doses.[9]

Glucose oxidase is also produced by the hypopharyngeal glands of honeybee workers and deposited into honey where it acts as a natural preservative. GOx at the surface of the honey reduces atmospheric O2 to hydrogen peroxide (H2O2), which acts as an antimicrobial barrier.[10]


Glucose oxidase enzyme powder from Aspergillus niger.

GOx is a dimeric protein, the 3D structure of which has been elucidated. The active site where glucose binds is in a deep pocket. The enzyme, like many proteins that act outside of cells, is covered with carbohydrate chains. GOx is a glucose oxidising enzyme with a molecular weight of 160 kDa. It is a dimeric glycoprotein consisting of two subunits each weighing 80 kDa. Flavinadenine dinucleotide (FAD) in the active site is buried approximately 1.5 nm inside the protein shell and acts as the initial electron acceptor.[11]


At pH 7, glucose exists in solution in cyclic hemiacetal form as 63.6% β-D-glucopyranose and 36.4% α-D-glucopyranose, the proportion of linear and furanose form being negligible. The glucose oxidase binds specifically to β-D-glucopyranose and does not act on α-D-glucose. It oxidises all of the glucose in solution because the equilibrium between the α and β anomers is driven towards the β side as it is consumed in the reaction.[3]

Glucose oxidase catalyzes the oxidation of β-D-glucose into D-glucono-1,5-lactone, which then hydrolyzes into gluconic acid.

In order to work as a catalyst, GOx requires a coenzyme, flavin adenine dinucleotide (FAD). FAD is a common component in biological oxidation-reduction (redox) reactions. Redox reactions involve a gain or loss of electrons from a molecule. In the GOx-catalyzed redox reaction, FAD works as the initial electron acceptor and is reduced to FADH.[12] Then FADH is oxidized by the final electron acceptor, molecular oxygen (O2), which can do so because it has a higher reduction potential. O2 is then reduced to hydrogen peroxide (H2O2).


Glucose monitoring[edit]

Glucose oxidase is widely used coupled to peroxidase reaction that visualizes colorimetrically the formed H2O2, for the determination of free glucose in sera or blood plasma for diagnostics, using spectrometric assays manually or with automated procedures, and even point-of-use rapid assays.[3][8]

Similar assays allows the monitoring of glucose levels in fermentation, bioreactors, and to control glucose in vegetal raw material and food products.[citation needed] In the glucose oxidase assay, the glucose is first oxidized, catalyzed by glucose oxidase, to produce gluconate and hydrogen peroxide. The hydrogen peroxide is then oxidatively coupled with a chromogen to produce a colored compound which may be measured spectroscopically. For example, hydrogen peroxide together with 4 amino-antipyrene (4-AAP) and phenol in the presence of peroxidase yield a red quinoeimine dye that can be measured at 505 nm. The absorbance at 505 nm is proportional to concentration of glucose in the sample.

Enzymatic glucose biosensors use an electrode instead of O2 to take up the electrons needed to oxidize glucose and produce an electronic current in proportion to glucose concentration.[13] This is the technology behind the disposable glucose sensor strips used by diabetics to monitor serum glucose levels.[14]

Food preservation[edit]

In manufacturing, GOx is used as an additive thanks to its oxidizing effects: it prompts for stronger dough in baking, replacing oxidants such as bromate.[15] It is also used as a food preservative to help remove oxygen and glucose from food when packaged such as dry egg powder to prevent unwanted browning and undesired taste.[16]

Wound treatment[edit]

Wound care products, such as "Flaminal Hydro" make use of an alginate hydrogel containing glucose oxidase and other components as an oxidation agent.

Clinical trials[edit]

A nasal spray from a bag-on-valve device that mixes glucose oxidase with glucose has undergone clinical trials in 2016 for the prevention and treatment of the common cold.[17][18][19]

See also[edit]


  1. ^ PDB: 1gpe​; Goodsell D (May 2006). "Molecule of the Month: Glucose Oxidase". RCSB Protein Data Bank. doi:10.2210/rcsb_pdb/mom_2006_5.
  2. ^ a b Wong CM, Wong KH, Chen XD (Apr 2008). "Glucose oxidase: natural occurrence, function, properties and industrial applications". Applied Microbiology and Biotechnology. 78 (6): 927–938. doi:10.1007/s00253-008-1407-4. PMID 18330562. S2CID 2246466.
  3. ^ a b c "Glucose Oxidase Technical sheet" (PDF). Interchim.[permanent dead link]
  4. ^ Ghoshdastider U, Xu R, Trzaskowski B, Mlynarczyk K, Miszta P, Viswanathan S, Renugopalakrishnan V, Filipek S (2015). "Molecular Effects of Encapsulation of Glucose Oxidase Dimer by Graphene". RSC Advances. 5 (18): 13570–8. Bibcode:2015RSCAd...513570G. doi:10.1039/C4RA16852F.
  5. ^ "Detlev Müller discovers glucose oxidase". Archived from the original on 18 April 2018. Retrieved 13 June 2017.{{cite web}}: CS1 maint: unfit URL (link)
  6. ^ a b Coulthard CE, Michaelis R, Short WF, Sykes G (1945). "Notatin: an anti-bacterial glucose-aerodehydrogenase from Penicillium notatum Westling and Penicillium resticulosum sp. nov". The Biochemical Journal. 39 (1): 24–36. doi:10.1042/bj0390024. PMC 1258144. PMID 16747849.
  7. ^ Keilin D, Hartree EF (Jan 1952). "Specificity of glucose oxidase (notatin)". The Biochemical Journal. 50 (3): 331–41. doi:10.1042/bj0500331. PMC 1197657. PMID 14915954.
  8. ^ a b Raba J, Mottola HA (1995). "Glucose Oxidase as an Analytical Reagent" (PDF). Critical Reviews in Analytical Chemistry. 25 (1): 1–42. doi:10.1080/10408349508050556.
  9. ^ a b Broom WA, Coulthard CE, Gurd MR, Sharpe ME (Dec 1946). "Some pharmacological and chemotherapeutic properties of notatin". British Journal of Pharmacology and Chemotherapy. 1 (4): 225–233. doi:10.1111/j.1476-5381.1946.tb00041.x. PMC 1509745. PMID 19108091.
  10. ^ Bucekova M, Valachova I, Kohutova L, Prochazka E, Klaudiny J, Majtan J (Aug 2014). "Honeybee glucose oxidase--its expression in honeybee workers and comparative analyses of its content and H2O2-mediated antibacterial activity in natural honeys". Die Naturwissenschaften. 101 (8): 661–670. Bibcode:2014NW....101..661B. doi:10.1007/s00114-014-1205-z. PMID 24969731. S2CID 16338921.
  11. ^ Mano, Nicolas (2019). "Engineering glucose oxidase for bioelectrochemical applications". Bioelectrochemistry. 128: 218-240.
  12. ^ Sanner, Christoph; et al. (March 1991). "15N‐ and 13C‐NMR investigations of glucose oxidase from Aspergillus niger". European Journal of Biochemistry. 196 (3): 663–672. doi:10.1111/j.1432-1033.1991.tb15863.x. PMID 2013289.
  13. ^ Blanford CF (Dec 2013). "The birth of protein electrochemistry". Chemical Communications. Royal Society of Chemistry. 49 (95): 11130–11132. doi:10.1039/C3CC46060F. PMID 24153438.
  14. ^ Cass AE, Davis G, Francis GD, Hill HA, Aston WJ, Higgins IJ, Plotkin EV, Scott LD, Turner AP (Apr 1984). "Ferrocene-mediated enzyme electrode for amperometric determination of glucose". Analytical Chemistry. American Chemical Society. 56 (4): 667–671. doi:10.1021/ac00268a018. PMID 6721151.
  15. ^ Wong CM, Wong KH, Chen XD (April 2008). "Glucose oxidase: natural occurrence, function, properties and industrial applications". Applied Microbiology and Biotechnology. 78 (6): 927–38. doi:10.1007/s00253-008-1407-4. PMID 18330562. S2CID 2246466.
  16. ^ Dubey MK, Zehra A, Aamir M, Meena M, Ahirwal L, Singh S, et al. (2017). "Improvement Strategies, Cost Effective Production, and Potential Applications of Fungal Glucose Oxidase (GOD): Current Updates". Frontiers in Microbiology. 8: 1032. doi:10.3389/fmicb.2017.01032. PMC 5468390. PMID 28659876.
  17. ^ Clinical trial number NCT01883427 for "Nasal Spray With Glucose Oxidase Preventing Common Cold in Pre-school Children" at
  18. ^ Clinical trial number NCT01883440 for "Glucose Oxidase as Treatment Against Common Cold" at
  19. ^ Clinical trial number NCT01883453 for "A Nasal Spray With Glucose Oxidase as a Treatment of Common Cold" at

External links[edit]