Regulation of methylotrophy in Paracoccus denitrificans

Paracoccus denitrificans is a long-established model organism for studies of methylotrophy, the use of one-carbon compounds as sources of energy and carbon. P. denitrificans can use methanol and methylamine as growth substrates, oxidizing both to formaldehyde in the periplasm. Formaldehyde is oxidized to formate and then to carbon dioxide, which is assimilated into biomass via the Calvin cycle. Genes required for the oxidation of methanol, methylamine, formaldehyde and formate are typically expressed only under methylotrophic conditions or during growth on multi-carbon substrates (such as choline) the catabolism of which generates formaldehyde as a product of demethylation reactions. In this article, we review the pathways of methylotrophic metabolism and the proteins involved, before focusing on mechanisms of gene regulation. P. denitrificans has genes encoding calcium- and lanthanide-dependent methanol dehydrogenases. In other methylotrophs, expression of these enzymes is subject to reciprocal regulation according to the presence or absence of lanthanide ions in growth media. This regulatory phenomenon is referred to as the 'lanthanide switch'. We propose a model for the mechanism of the lanthanide switch in P. denitrificans, which extrapolates from relevant information in other methylotrophs and is consistent with prior literature.