Methanol dehydrogenase

PQQ-MDH enzyme structure, with PQQ in the center. The yellow sphere represents a La³⁺ ion.

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.

Classes of Methanol Dehydrogenase

Shows the reaction of methanol to formaldehyde catalyzed by MDH.

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(EC 1.1.1.244) 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 methylotrophs, 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.

Further reading

• Arfman N, Watling EM, Clement W, van Oosterwijk RJ, de Vries GE, Harder W, et al. (1989). "Methanol metabolism in thermotolerant methylotrophic Bacillus strains involving a novel catabolic NAD-dependent methanol dehydrogenase as a key enzyme". Archives of Microbiology. 152 (3): 280–288. doi:10.1007/BF00409664. PMID 2673121.