This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: mycothiol-dependent formaldehyde detoxification
|Superclasses:||Degradation/Utilization/Assimilation → C1 Compounds Utilization and Assimilation → Formaldehyde Oxidation|
Expected Taxonomic Range:
The detoxification of the highly toxic formaldehyde is a major biochemical necessity for most life forms. In the case of methylotrophic bacteria, formaldehyde is not just a toxic compound, but also a central intermediate. It has been suggested that the formaldehyde concentration in the cytoplasm of a methylotroph would rise to 100mM in less than 1 minute if formaldehyde consumption would stop [Vorholt00]. Several different pathways for Formaldehyde Oxidation are known in bacteria, encoded by unrelated or distantly related genes.
About This Pathway
Even though glutathione is almost a universal thiol, present in eukaryotes, Gram negative bacteria, and several Gram positive bacteria, there are some organisms that produce alternative thiols. One such group is the actinomycetes, including the mycobacteria, which produce the unique compound mycothiol as their main thiol (see the pathway mycothiol biosynthesis). In these organisms a new type of formaldehyde dehydrogenase was discovered, which is specific to mycothiol as its cofactor [Eggeling85, vanOphem92, MissetSmits97]. This enzyme catalyzes a very similar reaction to the glutathione dependent enzyme NAD- and glutathione-dependent formaldehyde dehydrogenase. S-hydroxymethylmycothiol, which is formed spontaneously by mycothiol and formaldehyde, is oxidized to S-formylmycothiol in the presence of NAD+. The product is then hydrolyzed to formate and mycothiol [Vogt03]. It is still not known whether the hydrolysis is catalyzed enzymatically.
Eggeling85: Eggeling L, Sahm H (1985). "The formaldehyde dehydrogenase of Rhodococcus erythropolis, a trimeric enzyme requiring a cofactor and active with alcohols." Eur J Biochem 150(1);129-34. PMID: 3160586
MissetSmits97: Misset-Smits M, van Ophem PW, Sakuda S, Duine JA (1997). "Mycothiol, 1-O-(2'-[N-acetyl-L-cysteinyl]amido-2'-deoxy-alpha-D-glucopyranosyl)-D- myo-inositol, is the factor of NAD/factor-dependent formaldehyde dehydrogenase." FEBS Lett 409(2);221-2. PMID: 9202149
vanOphem92: van Ophem PW, Van Beeumen J, Duine JA (1992). "NAD-linked, factor-dependent formaldehyde dehydrogenase or trimeric, zinc-containing, long-chain alcohol dehydrogenase from Amycolatopsis methanolica." Eur J Biochem 206(2);511-8. PMID: 1597190
Vogt03: Vogt RN, Steenkamp DJ, Zheng R, Blanchard JS (2003). "The metabolism of nitrosothiols in the Mycobacteria: identification and characterization of S-nitrosomycothiol reductase." Biochem J 374(Pt 3);657-66. PMID: 12809551
Vorholt00: Vorholt JA, Marx CJ, Lidstrom ME, Thauer RK (2000). "Novel formaldehyde-activating enzyme in Methylobacterium extorquens AM1 required for growth on methanol." J Bacteriol 182(23);6645-50. PMID: 11073907
Norin97: Norin A, Van Ophem PW, Piersma SR, Persson B, Duine JA, Jornvall H (1997). "Mycothiol-dependent formaldehyde dehydrogenase, a prokaryotic medium-chain dehydrogenase/reductase, phylogenetically links different eukaroytic alcohol dehydrogenases--primary structure, conformational modelling and functional correlations." Eur J Biochem 248(2);282-9. PMID: 9346279
Spies94: Spies HS, Steenkamp DJ (1994). "Thiols of intracellular pathogens. Identification of ovothiol A in Leishmania donovani and structural analysis of a novel thiol from Mycobacterium bovis." Eur J Biochem 224(1);203-13. PMID: 8076641
Tessman85: Tessman ES, Peterson P (1985). "Plaque color method for rapid isolation of novel recA mutants of Escherichia coli K-12: new classes of protease-constitutive recA mutants." J Bacteriol 163(2);677-87. PMID: 3160686
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