Table 3.
Functionally characterized F420H2-dependent reductases. This table updates and expands upon the enzymes previously summarized and reviewed by Greening et al. (2016).
| Oxidoreductase and domain | Physiological role | Taxonomic distribution | Family | EC no. | PDB ID | References |
|---|---|---|---|---|---|---|
| Archaea | ||||||
| Mtd: F420-reducing methylene-H4MPT dehydrogenase | Reduces CH≡H4MPT to CH2=H4MPT with F420H2 during CO2-reducing methanogenesis. Performs the opposite reaction during methylotrophic methanogenesis and anaerobic methane/alkane oxidation. | Various Euryarchaeota including: all orders of methanogens, Archaeoglobales, ANME and Halobacteriales; various TACK and Asgard archaea | Mtd | 1.5.98.1 | 1QV9, 1U6I, 3IQF, 3IQE | Hartzell et al. (1985); Te Brömmelstroet et al. (1991a,b); Hagemeier et al. (2003a,b); Ceh et al. (2009) |
| Mer: F420H2-dependent methylene-H4MPT reductase | Reduces CH2=H4MPT to CH3-H4MPT with F420H2 during CO2-reducing methanogenesis. Performs the opposite reaction during methylotrophic methanogenesis and anaerobic methane/alkane oxidation. | Various Euryarchaeota including: all orders of methanogens, Archaeoglobales, ANME and Halobacteriales; various TACK and Asgard archaea | LLHT | 1.5.98.2 | 1F07, 1EZW, 1Z69 | Te Brömmelstroet et al. (1991b); Shima et al. (2000); Aufhammer et al. (2005); Ceh et al. (2009) |
| Fpo: F420H2-dependent methanophenazine reductase | Proton-translocating primary dehydrogenase in respiratory chain transferring electrons from F420H2 to heterodisulfide. | Methanosarcinales | FDRC | 1.1.98.4 | Bäumer et al. (1998); Deppenmeier, Lienard and Gottschalk (1999); Ide, Bäumer and Deppenmeier (1999); Bäumer et al. (2000); Welte and Deppenmeier (2011a) | |
| Fqo: F420H2-dependent quinone reductase | Proton-translocating primary dehydrogenase in respiratory chain transferring electrons from F420H2 to sulfate. | Archaeoglobales and ANME | FDRC | 1.1.98.4 | KUNOW et al. (1994); Brüggemann, Falinski and Deppenmeier (2000); Hallam et al. (2004); Hocking et al. (2014) | |
| Fpr: F420H2-dependent oxidase | Detoxifies O2 by mediating the four-electron reduction of O2 to H2O with F420H2. | Methanobacteriales, Methanococcales, Methanomicrobiales and Methanocellales | FprA | 1.5.3.22 | 2OHH, 2OHI, 2OHJ | Seedorf et al. (2004,2007) |
| Fsr: F420H2-dependent sulfite reductase | Detoxifies sulfite by mediating the six electron reduction of sulfite to sulfide with F420H2. Also enables the use of sulfite as an S source. | Methanobacteriales and Methanococcales | FDRC | 1.8.98.3 | Johnson and Mukhopadhyay (2005, 2008a) | |
| Fno: F420H2-dependent NADP+ reductase | Exchanges electrons between NADP and F420. NADP+ reduction direction dominant in archaea, as NADP is the secondary cofactor. | Various Euryarchaeota including: all orders of methanogens, Archaeoglobales and ANME; various TACK and Asgard archaea | Fno | 1.5.1.40 | 1JAY, 1JAX | Tzeng, Wolfe and Bryant (1975); Kunow et al. (1993); Berk and Thauer (1997); Warkentin et al. (2001) |
| HdrA2B2C2: F420H2-dependent, electron-bifurcating, heterodisulfide reductase | The HdrA2 subunit of this complex oxidizes F420H2, with subunits HdrB2 and HdrC2 bifurcating the resulting electrons to ferredoxin and CoM-S-S-CoB (heterodisulfide). Thought to mediate energy conservation during acetoclastic methanogenesis. | Methanosarcinales | HdrA2 | Yan, Wang and Ferry (2017) | ||
| DFTR: F420H2-dependent thioredoxin reductase | Recycling of the thioredoxin disulfide through reduction by electrons transferred from F420H2, via a low potential FMN and disulfide redox center. | Methanococcales | DFTR | 1.8.1.9 | Susanti, Loganathan and Mukhopadhyay (2016) | |
| Bacteria | ||||||
| Ddn: F420H2-dependent menaquinone reductase | Reduction of the respiratory cofactor menaquinone for energy conservation and possibly to mitigate redox stress. Also catalyzes the promiscuous activation nitroimidazole prodrugs. FDOR-A1 family. | Most Actinomycetales (e.g., Mycobacterium, Streptomyces, Rhodococcus), Chloroflexi?, Methanosarcinales? | FDOR-A | 1.1.98.- | 3H96, 4Y9I, 3R5R, 3R57 | Taylor et al. (2010); Cellitti et al. (2012); Gurumurthy et al. (2013); Ahmed et al. (2015); Lee et al. (2020) |
| Fbr: F420H2-dependent biliverdin reductase | Reduction of the heme degradation product biliverdin to bilirubin. May also reduce mycobillins. FDOR-B3 and FDOR-B4 family. | Most Actinomycetales (e.g., Mycobacterium, Streptomyces, Rhodococcus), Chloroflexi? | FDOR-B | 2ASF, 4QVB, 1W9A | Canaan et al. (2005); Biswal et al. (2006); Ahmed et al. (2015, 2016); Mashalidis et al. (2015) | |
| Fts: F420H2-dependent tetracycline synthase | Reduction of dehydrotetracyclines to tetracyclines during streptomycete antibiotic synthesis. Role in mycobacteria unknown. FDOR-B1 family. | Most Actinomycetales (e.g., Mycobacterium, StreptomycesandRhodococcus), Chloroflexi?, Thaumarchaeota? | FDOR-B | Taylor et al. (2010); Wang et al. (2013); Ahmed et al. (2015) | ||
| TpnL: F420H2–dependent dehydropiperidine reductase | Reduction of the dehydropiperidine moiety to piperidine during the synthesis of thiopeptins antibiotics. FDOR-B family. | Some Actinomycetales (Streptomyces, Amycolatopsis, Micromonospora and Actinoalloteichus) | FDOR-B | Ichikawa, Bashiri and Kelly (2018) | ||
| GupA: F420H2–dependent dihydropyrazine reductase | Reduction of the dihydropyrazine ring to piperzine during the synthesis of guanipiperazines. FDOR-B family. | Some Actinomycetales (Streptomyces) | FDOR-B | Shi et al. (2021) | ||
| Other F420H2-dependent flavin/deazaflavin oxidoreductases (FDORs) | Physiological substrates of A2-A4, B1, B2, B5, B6, AA1- AA5 families unknown. Promiscuous reductase activity observed towards multiple chemical classes that may facilitate detoxification. AA1s may be fatty acid saturases. | Most Actinomycetales (e.g., Mycobacterium, Streptomyces and Rhodococcus), Chloroflexi?, Halobacteriales? | FDOR-A/B | 3F7E, 1RFE, 4ZKY | Lapalikar et al. (2012); Ahmed et al. (2015); Jirapanjawat et al. (2016); Greening et al. (2017) | |
| Fht: F420H2-dependent picrate reductase | Reduces 2,4,6-trinitrophenol (picrate) for use as a C and N source through hydride transfer to the nitroaromatic ring. | Few Actinomycetales (Rhodococcus, Nocardia, Nocardioides) | LLHT | Ebert, Rieger and Knackmuss (1999); Heiss et al. (2002) | ||
| Fps/Adp6: F420H2-dependent 4-alkyl-L-proline derivative reductases | Reduction of 4-alkyl-L-proline derivatives (APDs) in the final step in the biosynthesis of this compound. Different enzymes of this class impart structural diversity by reducing either the endocyclic imine or the exocyclic double bond of APDs. | Some Actinomycetales (Streptomyces, Micrococcus and Streptosporangium) | LLHT | Li et al. (2009a,b); Steiningerova et al. (2020) | ||
| fPKR: F420H2-dependent phthiodiolone ketoreductase | Reduction of phthiodiolone keto intermediates during the synthesis of phthiocerol dimycocerosates (PDIM), a class of mycobacterial cell surface apolar lipids. | Few Mycobacterium (primarily pathogenic species) | LLHT | Purwantini, Daniels and Mukhopadhyay (2016) | ||
| LxmJ: F420H2-dependent 2,3-didehydroalanine reductase | Stereospecific reduction of the 2,3-didehydroalanine reductase to D-alanine during class V lanthipeptide biosynthesis | Few Streptomyces | LLHT | Tao et al. (2020) | ||
| Other H2-dependent luciferase-like hydride transferases (LLHTs) | Unknown. Likely to have diverse roles in endogenous and exogenous redox metabolism of organic compounds. | Most Actinomycetales (e.g., Mycobacterium, StreptomycesandRhodococcus) | LLHT |