Coenzyme F420

Last updated
Coenzyme F420
F420.svg
Names
IUPAC name
(2S)-2-[[(4S)-4-carboxy-4-[[(2S)-2-[hydroxy-[(2R,3S,4S)-2,3,4-trihydroxy-5-(2,4,8-trioxo-1H-pyrimido[4,5-b]quinolin-10-yl)pentoxy]phosphoryl]oxypropanoyl]amino]butanoyl]amino]pentanedioic acid
Other names
Coenzyme F(420); F420
Identifiers
3D model (JSmol)
ECHA InfoCard 100.110.762 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
  • C[C@@H](C(=O)N[C@@H](CCC(=O)N[C@@H](CCC(=O)O)C(=O)O)C(=O)O)OP(=O)(O)OC[C@H]([C@H]([C@H](CN1C2=CC(=O)C=CC2=CC3=C1NC(=O)NC3=O)O)O)O
Properties
C29H36N5O18P
Molar mass 773.598 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Coenzyme F420 is a family of coenzymes involved in redox reactions in a number of bacteria and archaea. It is derived from coenzyme FO (7,8-didemethyl-8-hydroxy-5-deazariboflavin) and differs by having a oligoglutamyl tail attached via a 2-phospho-L-lactate bridge. F420 is so named because it is a flavin derivative with an absorption maximum at 420 nm.

Contents

F420 was originally discovered in methanogenic archaea [1] and in Actinomycetota (especially in Mycobacterium ). [2] It is now known to be used also by Cyanobacteria and by soil Proteobacteria, Chloroflexi and Firmicutes. [3] Eukaryotes including the fruit fly Drosophila melanogaster and the algae Ostreococcus tauri also use Coenzyme FO. [4]

F420 is structurally similar to FMN, but catalytically it is similar to NAD and NADP: it has low redox potential and always transfer a hydride. As a result, it is not only a versatile cofactor in biochemical reactions, but also being eyed for potential as an industrial catalyst. Similar to FMN, it has two states: one reduced state, notated as F420-H2, and one oxidized state, written as just F420. [5] FO has largely similar redox properties, but cannot carry an electric charge and as a result probably slowly leaks out of the cellular membrane. [3]

A number of F420 molecules, differing by the length of the oligoglutamyl tail, are possible; F420-2, for example, refers to the version with two glutamyl units attached. Lengths from 4 to 9 are typical. [3]

Biosynthesis

Coenzyme F420 is synthesized via a multi-step pathway:

Oxidized F420 can be converted to reduced F420-H2 by multiple enzymes such as Glucose-6-phosphate dehydrogenase (coenzyme-F420) (Fgd1). [5]

Function

The coenzyme is a substrate for coenzyme F420 hydrogenase, [6] 5,10-methylenetetrahydromethanopterin reductase and methylenetetrahydromethanopterin dehydrogenase. [7] [8]

A long list of other enzymes use F420 to oxidize (dehydrogenate) or F420-H2 to reduce substrates. [5]

F420 plays a central role in redox reactions across diverse organisms, including archaea and bacteria, by participating in methanogenesis, antibiotic biosynthesis, DNA repair and the activation of antitubercular drugs. Its ability to carry out hydride transfer reactions is enabled by its low redox potential, which is optimized for specific biochemical pathway. [9] [10] [11]

Clinical relevance

Delamanid, a drug used to treat multi-drug-resistant tuberculosis (MDRTB) in combination with other antituberculosis medications, is activated in the mycobacterium by deazaflavin-dependent nitroreductase (Ddn), an enzyme which uses dihydro-F420 (reduced form). The activated form of the drug is highly reactive and attacks cell wall synthesis enzymes such as DprE2. Pretomanid works in the same way. Clinical isolates resistant to these two drugs tend to have mutations in the biosynthetic pathway for F420. [12]

See also

Related Research Articles

<span class="mw-page-title-main">Nicotinamide adenine dinucleotide</span> Chemical compound which is reduced and oxidized

Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other, nicotinamide. NAD exists in two forms: an oxidized and reduced form, abbreviated as NAD+ and NADH (H for hydrogen), respectively.

Methanogens are anaerobic archaea that produce methane as a byproduct of their energy metabolism, i.e., catabolism. Methane production, or methanogenesis, is the only biochemical pathway for ATP generation in methanogens. All known methanogens belong exclusively to the domain Archaea, although some bacteria, plants, and animal cells are also known to produce methane. However, the biochemical pathway for methane production in these organisms differs from that in methanogens and does not contribute to ATP formation. Methanogens belong to various phyla within the domain Archaea. Previous studies placed all known methanogens into the superphylum Euryarchaeota. However, recent phylogenomic data have led to their reclassification into several different phyla. Methanogens are common in various anoxic environments, such as marine and freshwater sediments, wetlands, the digestive tracts of animals, wastewater treatment plants, rice paddy soil, and landfills. While some methanogens are extremophiles, such as Methanopyrus kandleri, which grows between 84 and 110°C, or Methanonatronarchaeum thermophilum, which grows at a pH range of 8.2 to 10.2 and a Na+ concentration of 3 to 4.8 M, most of the isolates are mesophilic and grow around neutral pH.

<span class="mw-page-title-main">Pyrroloquinoline quinone</span> Chemical compound

Pyrroloquinoline quinone (PQQ), also called methoxatin, is a redox cofactor and antioxidant.

<span class="mw-page-title-main">Pyridoxal phosphate</span> Active form of vitamin B6

Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent activities, corresponding to ~4% of all classified activities. The versatility of PLP arises from its ability to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby stabilizing different types of carbanionic reaction intermediates.

<span class="mw-page-title-main">Nicotinamide adenine dinucleotide phosphate</span> Chemical compound

Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent ('hydrogen source'). NADPH is the reduced form, whereas NADP+ is the oxidized form. NADP+ is used by all forms of cellular life. NADP+ is essential for life because it is needed for cellular respiration.

<span class="mw-page-title-main">Flavin adenine dinucleotide</span> Redox-active coenzyme

In biochemistry, flavin adenine dinucleotide (FAD) is a redox-active coenzyme associated with various proteins, which is involved with several enzymatic reactions in metabolism. A flavoprotein is a protein that contains a flavin group, which may be in the form of FAD or flavin mononucleotide (FMN). Many flavoproteins are known: components of the succinate dehydrogenase complex, α-ketoglutarate dehydrogenase, and a component of the pyruvate dehydrogenase complex.

A hydrogenase is an enzyme that catalyses the reversible oxidation of molecular hydrogen (H2), as shown below:

<span class="mw-page-title-main">Coenzyme M</span> Chemical compound

Coenzyme M is a coenzyme required for methyl-transfer reactions in the metabolism of archaeal methanogens, and in the metabolism of other substrates in bacteria. It is also a necessary cofactor in the metabolic pathway of alkene-oxidizing bacteria. CoM helps eliminate the toxic epoxides formed from the oxidation of alkenes such as propylene. The structure of this coenzyme was discovered by CD Taylor and RS Wolfe in 1974 while they were studying methanogenesis, the process by which carbon dioxide is transformed into methane in some archaea. The coenzyme is an anion with the formula HSCH
2
CH
2
SO
3
. It is named 2-mercaptoethanesulfonate and abbreviated HS–CoM. The cation is unimportant, but the sodium salt is most available. Mercaptoethanesulfonate contains both a thiol, which is the main site of reactivity, and a sulfonate group, which confers solubility in aqueous media.

In enzymology, a coenzyme F420 hydrogenase (EC 1.12.98.1) is an enzyme that catalyzes the chemical reaction

In enzymology, a 5,10-methylenetetrahydromethanopterin reductase (EC 1.5.98.2) is an enzyme that catalyzes the chemical reaction

In enzymology, a methylenetetrahydromethanopterin dehydrogenase (EC 1.5.98.1) is an enzyme that catalyzes the chemical reaction

Methanocaldococcus jannaschii is a thermophilic methanogenic archaean in the class Methanococci. It was the first archaeon, and third organism, to have its complete genome sequenced. The sequencing identified many genes unique to the archaea. Many of the synthesis pathways for methanogenic cofactors were worked out biochemically in this organism, as were several other archaeal-specific metabolic pathways.

<span class="mw-page-title-main">Cofactor F430</span> Chemical compound

F430 is the cofactor (sometimes called the coenzyme) of the enzyme methyl coenzyme M reductase (MCR). MCR catalyzes the reaction EC 2.8.4.1 that releases methane in the final step of methanogenesis:

Glucose-6-phosphate dehydrogenase (coenzyme-F420) is an enzyme with systematic name D-glucose-6-phosphate:F420 1-oxidoreductase. This enzyme catalyses the following chemical reaction

7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase (EC 4.3.1.32, FO synthase) and 5-amino-6-(D-ribitylamino)uracil—L-tyrosine 4-hydroxyphenyl transferase (EC 2.5.1.147) are two enzymes always complexed together to achieve synthesis of FO, a precursor to Coenzyme F420. Their systematic names are 5-amino-5-(4-hydroxybenzyl)-6-(D-ribitylimino)-5,6-dihydrouracil ammonia-lyase (7,8-didemethyl-8-hydroxy-5-deazariboflavin-forming) and 5-amino-6-(D-ribitylamino)uracil:L-tyrosine, 4-hydroxyphenyl transferase respectively. The enzymes catalyse the following chemical reactions:

2-phospho-L-lactate transferase is an enzyme with systematic name (2S)-lactyl-2-diphospho-5'-guanosine:7,8-didemethyl-8-hydroxy-5-deazariboflavin 2-phospho-L-lactate transferase. This enzyme catalyses the following chemical reaction

Coenzyme F420-0:L-glutamate ligase (EC 6.3.2.31, CofE-AF, MJ0768, CofE) is an enzyme with systematic name L-glutamate:coenzyme F420-0 ligase (GDP-forming). This enzyme catalyses the following chemical reaction

Coenzyme F420-1:γ-L-glutamate ligase (EC 6.3.2.34, F420:gamma-glutamyl ligase, CofE-AF, MJ0768, CofE) is an enzyme with systematic name L-glutamate:coenzyme F420-1 ligase (GDP-forming). This enzyme catalyses the following chemical reaction

<i>Methanococcus maripaludis</i> Species of archaeon

Methanococcus maripaludis is a species of methanogenic archaea found in marine environments, predominantly salt marshes. M. maripaludis is a non-pathogenic, gram-negative, weakly motile, non-spore-forming, and strictly anaerobic mesophile. It is classified as a chemolithoautotroph. This archaeon has a pleomorphic coccoid-rod shape of 1.2 by 1.6 μm, in average size, and has many unique metabolic processes that aid in survival. M. maripaludis also has a sequenced genome consisting of around 1.7 Mbp with over 1,700 identified protein-coding genes. In ideal conditions, M. maripaludis grows quickly and can double every two hours.

Mycofactocin (MFT) is a family of small molecules derived from a peptide of the type known as RiPP (ribosomally synthesized and post-translationally modified peptides), naturally occurring in many types of Mycobacterium. It was discovered in a bioinformatics study in 2011. All mycofactocins share a precursor in the form of premycofactocin (PMFT); they differ by the cellulose tail added. Being redox active, both PMFT and MFT have an oxidized dione (mycofactocinone) form and a reduced diol (mycofactocinol) form, respectively termed PMFTH2 and MFTH2.

References

  1. Deppenmeier U (September 2002). "Redox-driven proton translocation in methanogenic Archaea". Cellular and Molecular Life Sciences. 59 (9): 1513–33. doi:10.1007/s00018-002-8526-3. PMC   11337502 . PMID   12440773. S2CID   23199201.
  2. Selengut JD, Haft DH (November 2010). "Unexpected abundance of coenzyme F(420)-dependent enzymes in Mycobacterium tuberculosis and other actinobacteria". Journal of Bacteriology. 192 (21): 5788–98. doi:10.1128/JB.00425-10. PMC   2953692 . PMID   20675471.
  3. 1 2 3 Ney, B; Ahmed, FH; Carere, CR; Biswas, A; Warden, AC; Morales, SE; Pandey, G; Watt, SJ; Oakeshott, JG; Taylor, MC; Stott, MB; Jackson, CJ; Greening, C (January 2017). "The methanogenic redox cofactor F(420) is widely synthesized by aerobic soil bacteria". The ISME Journal. 11 (1): 125–137. Bibcode:2017ISMEJ..11..125N. doi: 10.1038/ismej.2016.100 . PMC   5315465 . PMID   27505347.
  4. 1 2 Glas AF, Maul MJ, Cryle M, Barends TR, Schneider S, Kaya E, Schlichting I, Carell T (July 2009). "The archaeal cofactor F0 is a light-harvesting antenna chromophore in eukaryotes". Proceedings of the National Academy of Sciences of the United States of America. 106 (28): 11540–5. Bibcode:2009PNAS..10611540G. doi: 10.1073/pnas.0812665106 . PMC   2704855 . PMID   19570997.
  5. 1 2 3 Grinter, Rhys; Greening, Chris (8 September 2021). "Cofactor F420: an expanded view of its distribution, biosynthesis and roles in bacteria and archaea". FEMS Microbiology Reviews. 45 (5). doi: 10.1093/femsre/fuab021 . PMC   8498797 . PMID   33851978.
  6. Fox JA, Livingston DJ, Orme-Johnson WH, Walsh CT (July 1987). "8-Hydroxy-5-deazaflavin-reducing hydrogenase from Methanobacterium thermoautotrophicum: 1. Purification and characterization". Biochemistry. 26 (14): 4219–27. doi:10.1021/bi00388a007. PMID   3663585.
  7. Hagemeier CH, Shima S, Thauer RK, Bourenkov G, Bartunik HD, Ermler U (October 2003). "Coenzyme F420-dependent methylenetetrahydromethanopterin dehydrogenase (Mtd) from Methanopyrus kandleri: a methanogenic enzyme with an unusual quarternary structure". Journal of Molecular Biology. 332 (5): 1047–57. doi:10.1016/S0022-2836(03)00949-5. PMID   14499608.
  8. te Brömmelstroet BW, Geerts WJ, Keltjens JT, van der Drift C, Vogels GD (September 1991). "Purification and properties of 5,10-methylenetetrahydromethanopterin dehydrogenase and 5,10-methylenetetrahydromethanopterin reductase, two coenzyme F420-dependent enzymes, from Methanosarcina barkeri". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1079 (3): 293–302. doi:10.1016/0167-4838(91)90072-8. PMID   1911853.
  9. Purwantini, Endang; Loganathan, Usha; Mukhopadhyay, Biswarup (December 2018). Metcalf, William W. (ed.). "Coenzyme F 420 -Dependent Glucose-6-Phosphate Dehydrogenase-Coupled Polyglutamylation of Coenzyme F 420 in Mycobacteria". Journal of Bacteriology. 200 (23). doi:10.1128/JB.00375-18. ISSN   0021-9193. PMC   6222201 . PMID   30249701.
  10. Forouhar, Farhad; Abashidze, Mariam; Xu, Huimin; Grochowski, Laura L.; Seetharaman, Jayaraman; Hussain, Munif; Kuzin, Alexandre; Chen, Yang; Zhou, Weihong; Xiao, Rong; Acton, Thomas B.; Montelione, Gaetano T.; Galinier, Anne; White, Robert H.; Tong, Liang (April 2008). "Molecular Insights into the Biosynthesis of the F420 Coenzyme". Journal of Biological Chemistry. 283 (17): 11832–11840. doi: 10.1074/jbc.M710352200 . PMC   2431047 . PMID   18252724.
  11. Grinter, Rhys; Greening, Chris (2021-09-08). "Cofactor F420: an expanded view of its distribution, biosynthesis and roles in bacteria and archaea". FEMS Microbiology Reviews. 45 (5). doi:10.1093/femsre/fuab021. ISSN   1574-6976. PMC   8498797 . PMID   33851978.
  12. Abrahams, Katherine A.; Batt, Sarah M.; Gurcha, Sudagar S.; Veerapen, Natacha; Bashiri, Ghader; Besra, Gurdyal S. (28 June 2023). "DprE2 is a molecular target of the anti-tubercular nitroimidazole compounds pretomanid and delamanid". Nature Communications. 14 (1): 3828. Bibcode:2023NatCo..14.3828A. doi: 10.1038/s41467-023-39300-z . PMC   10307805 . PMID   37380634.