Thiols in formaldehyde dissimilation and detoxification

Duine, Johannis A.

doi:10.1002/biof.5520100217

Cited by 21 publications

(11 citation statements)

References 18 publications

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“…As formaldehyde is a toxic compound formed in classical metabolism at low concentrations as a result of demethylation reactions (Case and Benevenga, 1977), E. coli like other organisms possesses a formaldehyde detoxification pathway linked to glutathione (GSH) (Gonzalez et al, 2006;Gutheil et al, 1992) that involves a glutathione (GSH)-dependent formaldehyde dehydrogenase encoded by the gene frmA (Duine, 1999). Notably, this detoxification pathway is similar to the linear GSH-dependent formaldehyde oxidation pathways found in some methylotrophic organisms (Gonzalez et al, 2006;Gutheil et al, 1992).…”

Section: Engineering Strategymentioning

confidence: 99%

Engineering Escherichia coli for methanol conversion

Müller

Meyer

Litsanov

et al. 2015

Metabolic Engineering

172

233

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Section: Engineering Strategymentioning

confidence: 99%

Engineering Escherichia coli for methanol conversion

Müller

Meyer

Litsanov

et al. 2015

Metabolic Engineering

172

233

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“…Many organisms can further metabolize formaldehyde (7)(8), but for most the inherent reactivity of this compound makes it an undesirable byproduct of methyl group oxidation (9). In mitochondria and a significant proportion of bacteria, formaldehyde production is avoided by coupling amine oxidation to the synthesis of 5,10-methylenetetrahydrofolate (5,10-CH 2 -THF) 3 (5), thereby enabling transfer to the folate C 1 pool (1,10).…”

mentioning

confidence: 99%

An Internal Reaction Chamber in Dimethylglycine Oxidase Provides Efficient Protection from Exposure to Toxic Formaldehyde

Tralau

Lafite

Levy

et al. 2009

Journal of Biological Chemistry

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We report a synthetic biology approach to demonstrate substrate channeling in an unusual bifunctional flavoprotein dimethylglycine oxidase. The catabolism of dimethylglycine through methyl group oxidation can potentially liberate toxic formaldehyde, a problem common to many amine oxidases and dehydrogenases. Using a novel synthetic in vivo reporter system for cellular formaldehyde, we found that the oxidation of dimethylglycine is coupled to the synthesis of 5,10-methylenetetrahydrofolate through an unusual substrate channeling mechanism. We also showed that uncoupling of the active sites could be achieved by mutagenesis or deletion of the 5,10-methylenetetrahydrofolate synthase site and that this leads to accumulation of intracellular formaldehyde. Channeling occurs by nonbiased diffusion of the labile intermediate through a large solvent cavity connecting both active sites. This central "reaction chamber" is created by a modular protein architecture that appears primitive when compared with the sophisticated design of other paradigm substrate-channeling enzymes. The evolutionary origins of the latter were likely similar to dimethylglycine oxidase. This work demonstrates the utility of synthetic biology approaches to the study of enzyme mechanisms in vivo and points to novel channeling mechanisms that protect the cell milieu from potentially toxic reaction products.

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“…In the non‐methylotrophic Escherichia coli methanol oxidation requires glutathione and involves the S ‐formylglutathione hydrolases FrmB and YeiG and the glutathione‐dependent formaldehyde dehydrogenase FrmA as well as the formate dehydrogenase Fdh. In C. glutamicum either the mycothiol‐dependent formaldehyde dehydrogenase FadH or the NAD‐dependent acetaldehyde dehydrogenase Ald oxidizes formaldehyde to formate .…”

Section: Pathways Of Methanol Dissimilation and Assimilationmentioning

confidence: 99%

Methanol as carbon substrate in the bio‐economy: Metabolic engineering of aerobic methylotrophic bacteria for production of value‐added chemicals

Pfeifenschneider

Brautaset

Wendisch

2017

Biofuels Bioprod Bioref

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Bacteria are widely used as cell factories for production of enzymes and chemicals, mostly from sugars. Methylotrophic bacteria can utilize the one‐carbon compound methanol as sole carbon source for growth, and metabolic engineering is being used to develop bioprocesses based on these organisms for conversion of methanol into value‐added chemicals. Methylotrophic model strains include both Gram‐positive and Gram‐negative bacteria and in all cases methanol metabolism proceeds via the cell‐toxic intermediate formaldehyde. Thus, understanding the genetics, biochemistry, and regulation of methylotrophic pathways is crucial for successful strain development and for their concomitant fermentations. Also, such basic knowledge has proven useful for design of strategies and approaches for the rational transfer of methylotrophy into non‐methylotrophic bacteria. In the current review we highlight the best studied methylotrophic model organisms, with particular focus on the Gram‐positive Bacillus methanolicus and the Gram‐negative Methylobacterium extorquens, including their genetics and physiology. We present successful metabolic engineering examples leading to the construction of recombinant strains for the production of amino acids, platform chemicals, terpenoids and dicarboxylic acids derivatives from methanol as sole carbon source. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd

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Thiols in formaldehyde dissimilation and detoxification

Cited by 21 publications

References 18 publications

Engineering Escherichia coli for methanol conversion

Engineering Escherichia coli for methanol conversion

An Internal Reaction Chamber in Dimethylglycine Oxidase Provides Efficient Protection from Exposure to Toxic Formaldehyde

Methanol as carbon substrate in the bio‐economy: Metabolic engineering of aerobic methylotrophic bacteria for production of value‐added chemicals

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