Pathways & interactions
Formylmethanofuran dehydrogenase, subunit A (IPR012027)
Short name: Formylmethanofuran_DH_asu
Overlapping homologous superfamilies
- Metal-dependent hydrolase (IPR032466)
Formylmethanofuran dehydrogenase (EC:22.214.171.124) is found in methanogenic and sulphate-reducing archaea. The enzyme contains molybdenum or tungsten, a molybdopterin guanine dinuceotide cofactor (MGD) and iron-sulphur clusters [PMID: 8125106]. It catalyses the reversible reduction of CO2 and methanofuran via N-carboxymethanofuran (carbamate) to N-formylmethanofuran, the first and second steps in methanogenesis from CO2 [PMID: 8575452, PMID: 9342247]. This reaction is important for the reduction of CO2 to methane, in autotrophic CO2 fixation, and in CO2 formation from reduced C1 units [PMID: 8954165]. The synthesis of formylmethanofuran is crucial for the energy metabolism of archaea. Methanogenic archaea derives the energy for autrophic growth from the reduction of CO2 with molecular hydrogen as the electron donor [PMID: 12492476]. The process of methanogenesis consists of a series of reduction reactions at which the one-carbon unit derived from CO2 is bound to C1 carriers.
There are two isoenzymes of formylmethanofuran dehydrogenase: a tungsten-containing isoenzyme (Fwd) and a molybdenum-containing isoenzyme (Fmd). The tungsten isoenzyme is constitutively transcribed, whereas transcription of the molybdenum operon is induced by molybdate [PMID: 9818358]. The archaean Methanobacterium thermoautotrophicum contains a 4-subunit (FwdA, FwdB, FwdC, FwdD) tungsten formylmethanofuran dehydrogenase and a 3-subunit (FmdA, FmdB, FmdC) molybdenum formylmethanofuran dehydrogenase [PMID: 8954165].
This entry represents subunit A (FmdA and FwdA) of formylmethanofuran dehydrogenases. The other subunits are subunit B (IPR016457), subunit C (IPR017550), subunit D (IPR012040), subunit E (IPR026328), and subunit F. Some organisms also encode a fusion of the C and D subunits(IPR012048). Members of this entry share sequence similarity with the two highly conserved regions of dihydroorotase (PIRSF001238) (an amidohydrolase): the first is located at the N-terminal end and contains two histidine residues suggested to be involved in binding a zinc ion [PMID: 2570735]; the second conserved region is at the C terminus [PMID: 8672295].
In Methylobacterium extorquens, homologues of FmdA, FmdB and FmdC subunits were found and shown to copurify with a functional formyltransferase complex. However, there is no evidence that the complex catalyses the oxidation of formylmethanofuran [PMID: 11532013].
Methanogenic bacteria and archea derive the energy for autotrophic growth from methanogenesis, the reduction of CO2 with molecular hydrogen as the electron donor. FMDH catalyzes the first step in methanogenesis, the formyl-methanofuran synthesis. In this step, CO2 is bound to methanofuran and subsequently reduced to the formyl state with electrons derived from hydrogen [PMID: 2128800, PMID: 8672295].