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Wolfgang Buckel, Berta M. Martins, Albrecht Messerschmidt, Bernard T. Golding

Radical-mediated dehydration reactions in anaerobic bacteria

Keywords: amino acid fermentation, electron transfer, 2-enoyl-CoA, (R)-2-hydroxyacyl-CoA, 4-hydroxybutyryl-CoA, iron sulfur cluster

Most dehydratases catalyse the elimination of water from ?-hydroxy ketones, ?-hydroxy carboxylic acids or ?-hydroxyacyl-CoA. The electron-withdrawing carbonyl functionalities acidify the ?-hydrogens to enable their removal by basic amino acid side chains. Anaerobic bacteria, however, ferment amino acids via ?- or ?-hydroxyacyl-CoA, dehydrations of which involve the abstraction of a ?-hydrogen, which is ostensibly non-acidic (pK ca. 40). Evidence is accumulating that ?-hydrogens are acidified via transient conversion of the CoA derivatives to enoxy radicals by one-electron transfers, which decrease the pK to 14. The dehydrations of (R)-2-hydroxyacyl-CoA to (E)-2-enoyl-CoA are catalysed by heterodimeric [4Fe-4S]-containing dehydratases, which require reductive activation by an ATP-dependent one-electron transfer mediated by a homodimeric protein with a [4Fe-4S] cluster between the two subunits. The electron is further transferred to the substrate, yielding a ketyl radical anion, which expels the hydroxyl group and forms an enoxy radical. The dehydration of 4-hydroxybutyryl-CoA to crotonyl-CoA involves a similar mechanism, in which the ketyl radical anion is generated by one-electron oxidation. The structure of the FAD- and [4Fe-4S]-containing homotetrameric dehydratase is related to that of acyl-CoA dehydrogenases, suggesting a radical-based mechanism for both flavoproteins.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 386, 10/2005
Pages: 951 - 959

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