Coenzyme F<sub>420</sub> is a family of coenzymes involved in redox reactions in a number of bacteria and archaea. It is derived from coenzyme F<sub>O</sub> (7,8-didemethyl-8-hydroxy-5-deazariboflavin) and differs by having a oligoglutamyl tail attached via a 2-phospho-<small>L</small>-lactate bridge. F<sub>420</sub> is so named because it is a flavin derivative with an absorption maximum at 420 nm.
F<sub>420</sub> was originally discovered in methanogenic archaea and in Actinomycetota (especially in Mycobacterium). It is now known to be used also by Cyanobacteria and by soil Proteobacteria, Chloroflexi and Firmicutes. Eukaryotes including the fruit fly Drosophila melanogaster and the algae Ostreococcus tauri also use Coenzyme F<sub>O</sub>.
F<sub>420</sub> 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 F<sub>420</sub>-H<sub>2</sub>, and one oxidized state, written as just F<sub>420</sub>. F<sub>O</sub> has largely similar redox properties, but cannot carry an electric charge and as a result probably slowly leaks out of the cellular membrane.
A number of F<sub>420</sub> molecules, differing by the length of the oligoglutamyl tail, are possible; F<sub>420</sub>-2, for example, refers to the version with two glutamyl units attached. Lengths from 4 to 9 are typical.
Coenzyme F<sub>420</sub> is synthesized via a multi-step pathway:
Oxidized F<sub>420</sub> can be converted to reduced F<sub>420</sub>-H<sub>2</sub> by multiple enzymes such as Glucose-6-phosphate dehydrogenase (coenzyme-F420) (Fgd1).
The coenzyme is a substrate for coenzyme F<sub>420</sub> hydrogenase, 5,10-methylenetetrahydromethanopterin reductase and methylenetetrahydromethanopterin dehydrogenase.
A long list of other enzymes use F<sub>420</sub> to oxidize (dehydrogenate) or F<sub>420</sub>-H<sub>2</sub> to reduce substrates.
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.
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-F<sub>420</sub> (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 F<sub>420</sub>.