Methanol dehydrogenase

In enzymology, a methanol dehydrogenase (MDH) is an enzyme that catalyzes the chemical reaction:


 * CH3OH $$\rightleftharpoons$$ CH2O + 2 electrons + 2H+

How the electrons are captured and transported depends upon the kind of methanol dehydrogenase. There are three main types of MDHs: NAD+-dependent MDH, pyrrolo-quinoline quinone dependent MDH, and oxygen-dependent alcohol oxidase.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is methanol:NAD+ oxidoreductase. This enzyme participates in methane metabolism.

NAD+ Dependent MDH
A common electron acceptor in biological systems is nicotinamide adenine dinucleotide (NAD+); some enzymes use a related molecule called nicotinamide adenine dinucleotide phosphate (NADP+). An NAD+-dependent methanol dehydrogenase was first reported in a Gram-positive methylotroph and is an enzyme that catalyzes the chemical reaction:


 * CH3OH + NAD+ $$\rightleftharpoons$$ CH2O + NADH + H+

Thus, the two substrates of this enzyme are methanol and NAD+, whereas its 3 products are formaldehyde (CH2O), NADH, and H+. This can be performed under both aerobic and anaerobic conditions.

NAD+ -dependent MDHs are found in thermophilic, Gram positive methlyotrophs, but can also been obtained from some non-methylotrophic bacteria. NAD+-dependent MDHs have so far been found in Bacillus sp., Lysinibacillus sp.,and Cupriavidus sp.

PQQ-Dependent MDH
For Gram-negative bacteria, methanol oxidation occurs in the periplasmic space, facilitated by PQQ-dependent MDH. PQQ-dependent MDHs contain a PQQ prosthetic group, which has the role of capturing electrons from methanol oxidation and passing them to the cytochrome.

MxaFI and XoxF are the genes that encode for PQQ-dependent MDHs. In MxaFI-type MDH, calcium (Ca2+) is encoded as the cofactor for PQQ-dependent methylotrophy. XoxF-type MDHs use lanthanides (Ln3+) as cofactors and are highly selective towards early lanthanides (typically La-Nd). Sm3+, Eu3+, and Gd3+ can support some XoxF-type organisms, but less effectively. Pm3+ and Tb-Lu have shown no evidence of utilization so far.

Many methylotrophs encode both MxaFI and XoxF, but those that encode only one will encode exclusively for XoxF.

O2-Dependent Alcohol Oxidase
Oxygen-dependent alcohol oxidase (AOX) can be obtained from eukaryotic methylotrophs in the peroxisome of yeasts. Formaldehyde and hydrogen peroxide (H2O2) are formed through the oxidation of methanol. Dihydroxyacetone synthase (DAS) and catalase (CTA) must then transform these toxic chemicals into non-toxic forms to protect the cell. In this process, electrons from methanol are not captured as usable energy by the cell, and are thus lost.