Coenzyme F420

Source: Wikipedia, the free encyclopedia.
Structure of Coenzyme F420

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.

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

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]

Clinical relevance

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.[9]

See also

References

External links