Lanthanide-dependent methanol dehydrogenase

Lanthanide-dependent methanol dehydrogenase^[a] is an oxidoreductase enzyme involved in methane metabolic pathways in microbial metabolism. This enzyme was first isolated from the methylacidiphilum fumariolicum and others in the methylacidiphilum species. The enzyme requires La³⁺, Ce³⁺, Pr³⁺ or Nd³⁺. Higher lanthanides show decreasing activity with Sm³⁺, Eu³⁺ and Gd³⁺. The lanthanide atom in the enzyme is coordinated by pyrroloquinoline quinone.^[1] The enzyme catalyzes the following reaction

2 Fe(III)-cytochrome cL + methanol -> 2 Fe(II)-cytochrome cL + formaldehyde + 2 H⁺

Methylotrophic bacteria are those that consume one-carbon and methylated compounds as the primary carbon source. These bacteria have been known for a century and are largely important in methane and methanol biogeochemical cycles. For the majority of the history of studies on these enzymes, pyrroloquinoline quinone (PQQ)-dependent methanol dehydrogenases were said to be the primary enzymes for the oxidation of methanol.^[2] The machinery of the PQQ-dependent enzyme is largely Conserved among the α, β, and γ-protebacteria.

The discovery of lanthanide-dependent methanol dehydrogenases changed this belief, originally a seen as a homolog of MoxF. Several of these enzymes showed methanol dehydrogenase activity in the presence of lanthanide ions such as Ln³⁺. In the study of metaloenzymes, it was originally believed that Ln³⁺ was biologically unimportant, but the discovery of Ln³⁺-dependent AHDs revealed more about the biological activity of lanthanides.^[3][4]

In the homodimeric Ce³⁺-dependent methanol dehydrogenase sampled from methylacidiphilum fuimariolicum SolIV, the active site consists of glutamate, asparagine and aspartic acid residues that form a coordination complex for the Cerium ion. In protein crystallization studies, a molecule of polyethylene glycol occupies a substrate binding coordination position of Ce³⁺. The bacterial enzymes are known to interact with two cytochromes, c_L and c_H. Once methanol is oxidized, PQQ is reduced. The re-oxidation of PQQ is facilitated through the stepwise electron transfer to the cytochromes.^[5]

The reaction catalyzed by lanthanide-dependent methanol dehydrogenase is one that oxidizes methanol to form formaldehyde and hydrogen ions. The essential cofactors include a PQQ prosthetic group at the active site, in addition to essential cytochromes present for electron transfer. The enzyme acts at the CH-OH site.

MDHs in the methylobacterium species are typically shown to depend also on Ca²⁺ when grown on methanol. However, studies conducted with MDH on a methanol-substrate that were given only Ln³⁺ and not Ca³⁺ showed growth, indicating that MDHs (particularly Ln³⁺-dependent ones) can oxidize menthol and form formaldehyde even without calcium ions present.^[6]