Coenzyme F420 is a family ofcoenzymes involved inredox reactions in a number of bacteria and archaea. It is derived fromcoenzyme FO (7,8-didemethyl-8-hydroxy-5-deazariboflavin) and differs by having aoligoglutamyl tail attached via a 2-phospho-L-lactate bridge. F420 is so named because it is aflavin derivative with anabsorption maximum at 420 nm.
F420 is structurally similar toFMN, but catalytically it is similar toNAD andNADP: it has lowredox potential and always transfer ahydride. As a result, it is not only a versatile cofactor in biochemical reactions, but also being eyed for potential as anindustrial 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]
2-phospho-L-lactate transferase (FbiA) produces Coenzyme F420-0, the portion containing the head, the diphosphate bridge, and ending with a carboxylic acid group.
Coenzyme F420-1:gamma-L-glutamate ligase (other part ofFbiB) puts a gamma-glutamate residue at the -COOH end, producing Coenzyme F420-2, the final compound (in its oxidized form). Also responsible for adding additional units.
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]
Delamanid, a drug used to treatmulti-drug-resistant tuberculosis (MDRTB) in combination with other antituberculosis medications, is activated in the mycobacterium bydeazaflavin-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 asDprE2.Pretomanid works in the same way. Clinical isolates resistant to these two drugs tend to have mutations in the biosynthetic pathway for F420.[12]
^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.PMID3663585.
^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 [sic] structure".Journal of Molecular Biology.332 (5):1047–57.doi:10.1016/S0022-2836(03)00949-5.PMID14499608.
^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.PMID1911853.
