Assimilation, dissimilation, and detoxification of formaldehyde, a central metabolic intermediate of methylotrophic metabolism

Abstract

Methanol is a valuable raw material used in the manufacture of useful chemicals as well as a potential source of energy to replace coal and petroleum. Biotechnological interest in the microbial utilization of methanol has increased because it is an ideal carbon source and can be produced from renewable biomass. Formaldehyde, a cytotoxic compound, is a central metabolic intermediate in methanol metabolism. Therefore, microorganisms utilizing methanol have adopted several metabolic strategies to cope with the toxicity of formaldehyde. Formaldehyde is initially detoxified through trapping by some cofactors, such as glutathione, mycothiol, tetrahydrofolate, and tetrahydromethanopterin, before being oxidized to CO2. Alternatively, free formaldehyde can be trapped by sugar phosphates as the first reaction in the C1 assimilation pathways: the xylulose monophosphate pathway for yeasts and the ribulose monophosphate (RuMP) pathway for bacteria. In yeasts, although formaldehyde generation and consumption takes place in the peroxisome, the cytosolic formaldehyde oxidation pathway also plays a role in formaldehyde detoxification as well as energy formation. The key enzymes of the RuMP pathway are found in a variety of microorganisms including bacteria and archaea. Regulation of the genes encoding these enzymes and their catalytic mechanisms depend on the physiological traits of these organisms during evolution.

The Physiological Role of the Ribulose Monophosphate Pathway in Bacteria and Archaea

“…Therefore the fate of formaldehyde is central to understanding methylotrophic metabolism. 1) Because formaldehyde is highly cytotoxic, methylotrophic microorganisms have adopted several metabolic strategies to deal with the intracellular accumulation of this compound. 1,2) One such strategy is to trap formaldehyde with a cofactor, such as glutathione, mycothiol, tetrahydrofolate, or tetrahydromethanopterin, before it is oxidized to CO 2 .…”

“…1) Because formaldehyde is highly cytotoxic, methylotrophic microorganisms have adopted several metabolic strategies to deal with the intracellular accumulation of this compound. 1,2) One such strategy is to trap formaldehyde with a cofactor, such as glutathione, mycothiol, tetrahydrofolate, or tetrahydromethanopterin, before it is oxidized to CO 2 . Alternatively, free formaldehyde can be trapped by sugar phosphates as the first reaction in the C 1 assimilation pathways, the xylulose monophosphate pathway for yeasts and the ribulose monophosphate (RuMP) pathway for methylotrophic bacteria.…”

Molecular Basis of Methanol-Inducible Gene Expression and Its Application in the Methylotrophic YeastCandida boidinii

“…These results suggest that FGH and FDH are not essential but necessary for optimal growth on methanol. 2) In the wild-type formaldehyde oxidation pathway, 2 moles of NADH were generated from 1 mole of dissimilated formaldehyde. While 1 mole of NADH could be generated in the fgh1Á and fdh1Á strains, no NADH was formed in the fld1Á strain.…”

“…Formaldehyde is a central intermediate situated at the branch point between assimilatory and dissimilatory pathways. 2) A portion of formaldehyde is fixed to xylulose 5-phosphate (Xu5P) by dihydroxyacetone synthase (DAS) forming dihydroxyacetone (DHA) and glyceraldehyde 3-phosphate (GAP), which are used for the synthesis of cell constituents and the regeneration of Xu5P. AOD and DAS are localized to peroxisomes together with catalase (CTA), which decomposes H 2 O 2 .…”

“…A diverse range of prokaryotes and eukaryotes can utilize C 1 -compounds for growth and methylotrophs have a diverse range of metabolic pathways for assimilating and dissimilating C 1 -compounds. 1,2) In natural environments, methanol is produced by oxidation of methane by methane-oxidizing bacteria and also by decomposition of plant pectins and lignins that contain methylester and methoxyl groups, respectively, 3,4) and methanol is oxidized to CO 2 by methylotrophic bacteria and yeasts. Thus, methylotrophs play indispensable roles in the global carbon cycle between methane and CO 2 called ''the methane cycle.''…”