Radical-mediated dehydration reactions in anaerobic bacteria.
Most dehydratases catalyse the elimination of water from beta-hydroxy ketones, beta-hydroxy carboxylic acids or beta-hydroxyacyl-CoA. The electron-withdrawing carbonyl functionalities acidify the alpha-hydrogens to enable their removal by basic amino acid side chains. Anaerobic bacteria, however, ferment amino acids via alpha- or gamma-hydroxyacyl-CoA, dehydrations of which involve the abstraction of a beta-hydrogen, which is ostensibly non-acidic (pK ca. 40). Evidence is accumulating that beta-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.
Buckel
Wolfgang
W
Laboratorium für Mikrobiologie, Fachbereich Biologie, Philipps-Universität, D-35032 Marburg, Germany. buckel@staff.uni-marburg.de
Martins
Berta M
BM
Messerschmidt
Albrecht
A
Golding
Bernard T
BT
D000596:Amino Acids / Q000378:metabolism; D001421:Bacteria, Anaerobic / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D005285:Fermentation; D006836:Hydro-Lyases / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D014867:Water / Q000378:metabolism
D000596:Amino Acids; D001426:Bacterial Proteins; D014867:Water; D006836:Hydro-Lyases