Coenzyme F420

Coenzyme F420 is synthesized via a multi-step pathway: • 7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase (FbiC) produces Coenzyme FO (also written F0), itself a cofactor of DNA photolyase (antenna). This is the head portion of the molecule. • 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 F420-0:L-glutamate ligase (one part of FbiB) puts a glutamate residue at the -COOH end, producing Coenzyme F420-1. • Coenzyme F420-1:gamma-L-glutamate ligase (other part of FbiB) 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. Oxidized F420 can be converted to reduced F420-H2 by multiple enzymes such as Glucose-6-phosphate dehydrogenase (coenzyme-F420) (Fgd1). == Function ==

The coenzyme is a substrate for coenzyme F420 hydrogenase, 5,10-methylenetetrahydromethanopterin reductase and methylenetetrahydromethanopterin dehydrogenase. A long list of other enzymes use F420 to oxidize (dehydrogenate) or F420-H2 to reduce substrates. == 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. == See also ==