TABLE 2

Activity, role, and distribution of F420-dependent oxidoreductasesa

Oxidoreductase and domainPhysiological rolebTaxonomic distributioncDescriptionEC no.PDB IDReference(s)
F420-reducing dehydrogenases
    Archaea
        Frh: F420-reducing hydrogenaseHydrogenotrophic methanogenesis. Couples oxidation of H2 to reduction of F420. May be physiologically reversible.All orders of methanogensSection 3.2.11.12.98.14OMF, 4CI0, 3ZFS11, 16, 150, 219, 224, 227
        Ffd: F420-reducing formate dehydrogenaseFormatotrophic methanogenesis. Couples oxidation of formate to reduction of F420. May be part of the electron-bifurcating complex.Methanobacteriales, Methanococcales, Methanopyrales, Methanomicrobiales, MethanocellalesSection 3.2.21.2.99.917, 185, 190, 242, 259
        Adf: F420-reducing secondary alcohol dehydrogenaseGrowth on secondary alcohols. Couples oxidation of secondary alcohols (e.g., isopropanol) to reduction of F420.Methanomicrobiales, MethanocellalesSection 3.2.31.1.98.51RHC49, 271, 272
    Bacteria
        Fno: F420-reducing NADPH dehydrogenaseExchanges electrons between NADP and F420. F420 reduction important in bacteria, as F420 is the secondary cofactor.Many Actinomycetes (e.g., Streptomyces, Rhodococcus, Nocardia, Nocardioides), Αlpha- or Betaproteobacteria?Section 4.2.11.5.1.4012, 155
        Fgd: F420-reducing glucose-6-phosphate dehydrogenaseHeterotrophic growth. Couples oxidation of glucose-6-phosphate to reduction of F420 via the pentose phosphate pathway.Many Actinomycetes (e.g., Mycobacterium, Actinoplanes, Microbacterium, Amycolatopsis), Chloroflexi?Section 4.2.21.1.98.23B4Y163
        fHMAD: F420-reducing hydroxymycolic acid dehydrogenaseCell wall biosynthesis. Catalyzes F420-dependent oxidation of hydroxymycolic acids to ketomycolic acids.Few Mycobacterium (primarily pathogenic species)Section 4.2.3364, 365
F420H2-dependent reductases
    Archaea
        Mtd: F420-reducing methylene-H4MPT dehydrogenaseReduces CHEmbedded ImageH4MPT to CH2=H4MPT with F420H2 in methanogenesis. Reaction physiologically reversible.All orders of methanogens, Archaeoglobales, ANMESection 3.3.11.5.98.11QV9, 1U6I, 3IQF, 3IQE18, 47, 166, 275, 284, 285
        Mer: F420H2-dependent methylene-H4MPT reductaseReduces CH2=H4MPT to CH3-H4MPT with F420H2 in methanogenesis. Reaction physiologically reversible.All orders of methanogens, Archaeoglobales, ANME, HalobacterialesSection 3.3.11.5.98.21F07, 1EZW, 1Z6948, 159, 166, 284
        Fpo: F420H2-dependent methanophenazine reductaseProton-translocating primary dehydrogenase in respiratory chain transferring electrons from F420H2 to heterodisulfideMethanosarcinalesSection 3.3.21.1.98.4162, 304306, 327
        Fqo: F420H2-dependent quinone reductaseProton-translocating primary dehydrogenase in respiratory chain transferring electrons from F420H2 to sulfateArchaeoglobales, ANMESection 3.3.21.1.98.421, 198200
        Fpr: F420H2-dependent oxidaseDetoxifies O2 by mediating the four-electron reduction of O2 to H2O with F420H2Methanobacteriales, Methanococcales, Methanomicrobiales, MethanocellalesSection 3.3.31.5.3.222OHH, 2OHI, 2OHJ161, 192
        Fsr: F420H2-dependent sulfite reductaseDetoxifies sulfite by mediating the six-electron reduction of sulfite to sulfide with F420H2. Also enables use of sulfite as an S source.Methanobacteriales, MethanococcalesSection 3.3.41.8.98.351, 191
        Fno: F420H2-dependent NADP reductaseExchanges electrons between NADP and F420. NADP reduction important in archaea, as NADP is the secondary cofactor.All orders of methanogens, Archaeoglobales, ANMESection 3.3.51.5.1.401JAY, 1JAX16, 22, 160, 201
    Bacteria
        Ddn: F420H2-dependent nitroreductasesMay serve to detoxify redox cycling agents and other exogenous compounds. Also catalyze nitroimidazole activation.Most Actinomycetes (e.g., Mycobacterium, Streptomyces, Rhodococcus), Chloroflexi?, Methanosarcinales?Section 4.3.13H96, 4Y9I, 3R5R, 3R5728, 30, 32, 164
        Fbr: F420H2-dependent biliverdin reductasesReduce the heme degradation product biliverdin to bilirubin. May also reduce mycobillins. FDOR-B3 and -B4 family.Most Actinomycetes (e.g., Mycobacterium, Streptomyces, Rhodococcus), Chloroflexi?, Halobacteriales?Section 4.3.12ASF, 4QVB, 1W9A30, 165, 418, 419
        Fts: F420H2-dependent tetracycline synthasesReduce dehydrotetracyclines during streptomycete antibiotic synthesis. Role in mycobacteria unknown. FDOR-B1 family.Most Actinomycetes (e.g., Mycobacterium, Streptomyces, Rhodococcus), Chloroflexi?, Halobacteriales?Section 4.3.13F7E, 1RFE2830
        Other F420H2-dependent flavin/deazaflavin oxidoreductasesActivities of A2-A4, B1, B2, B5, B6, AA1-AA5 families unknown. AA1s may be fatty acid saturases.Most Actinomycetes (e.g., Mycobacterium, Streptomyces, Rhodococcus), Chloroflexi?, Halobacteriales?Section 4.3.14ZKY30, 55
        Fht: F420H2-dependent picrate reductasesReduces 2,4,6-trinitrophenol (picrate) for use as a C and N source through hydride transfer to the nitroaromatic ringFew Actinomycetes (Rhodococcus, Nocardia, Nocardioides)Section 4.3.254, 155
        Fps: F420H2-dependent tetrahydropyrrole synthasesReduces 4-propylidene-3,4-dihydropyrrole-2-carboxylate during biosynthesis of pyrrolobenzodiazepines antibioticsFew Actinomycetes (Streptomyces, Streptosporangium)Section 4.3.250, 389
        Other F420H2-dependent luciferase-like hydride transferasesUnknown. Likely to have diverse roles in endogenous and exogenous redox metabolism of organic compounds.Most Actinomycetes (e.g., Mycobacterium, Streptomyces, Rhodococcus)Section 4.3.2
  • a For more information about the enzymes, see the sections in the text where the enzymes are described, Enzyme Commission (EC) entries, Protein Data Bank structures, and key primary references.

  • b Note that several of F420-dependent reactions are physiologically reversible, including those catalyzed by Fno, Mtd, Mer, and possibly Frh. Fno is primarily an F420H2-dependent NADP reductase in methanogens and a F420-reducing NADPH dehydrogenase in bacteria; the enzyme appears to be similar in archaea and bacteria but is used in a different physiological context.

  • c Euryarchaeota are listed by order, namely, six methanogenic orders (Methanobacteriales, Methanococcales, Methanopyrales, Methanomicrobiales, Methanocellales, and Methanosarcinales) and two nonmethanogenic orders (Archaeoglobales and Halobacteriales). The various lineages of the uncultured anaerobic methanotrophic archaea are denoted as ANME. Actinobacteria are listed by genus (Mycobacterium, Streptomyces, Rhodococcus, Nocardia, Nocardioides, Streptosporangium, Microbacterium, Actinoplanes, and Amycolatopsis).