Dehydration of (R)-2-hydroxyacyl-CoA to enoyl-CoA in the fermentation of alpha-amino acids by anaerobic bacteria

FEMS Microbiol Rev. 2004 Oct;28(4):455-68. doi: 10.1016/j.femsre.2004.03.001.

Abstract

Several clostridia and fusobacteria ferment alpha-amino acids via (R)-2-hydroxyacyl-CoA, which is dehydrated to enoyl-CoA by syn-elimination. This reaction is of great mechanistic interest, since the beta-hydrogen, to be eliminated as proton, is not activated (pK 40-50). A mechanism has been proposed, in which one high-energy electron acts as cofactor and transiently reduces the electrophilic thiol ester carbonyl to a nucleophilic ketyl radical anion. The 2-hydroxyacyl-CoA dehydratases are two-component systems composed of an extremely oxygen-sensitive component A, an activator, and component D, the actual dehydratase. Component A, a homodimer with one [4Fe-4S]cluster, transfers an electron to component D, a heterodimer with 1-2 [4Fe-4S]clusters and FMN, concomitant with hydrolysis of two ATP. From component D the electron is further transferred to the substrate, where it facilitates elimination of the hydroxyl group. In the resulting enoxyradical the beta-hydrogen is activated (pK14). After elimination the electron is handed-over to the next incoming substrate without further hydrolysis of ATP. The helix-cluster-helix architecture of component A forms an angle of 105 degrees, which probably opens to 180 degrees upon binding of ATP resembling an archer shooting arrows. Therefore we designated component A as 'Archerase'. Here, we describe 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans, Clostridium symbiosum and Fusobacterium nucleatum, 2-phenyllactate dehydratase from Clostridium sporogenes, 2-hydroxyisocaproyl-CoA dehydratase from Clostridium difficile, and lactyl-CoA dehydratase from Clostridium propionicum. A relative of the 2-hydroxyacyl-CoA dehydratases is benzoyl-CoA reductase from Thauera aromatica. Analogous but unrelated archerases are the iron proteins of nitrogenase and bacterial protochlorophyllide reductase. In anaerobic organisms, which do not oxidize 2-oxo acids, a second energy-driven electron transfer from NADH to ferredoxin, the electron donor of component A, has been established. The transfer is catalysed by a membrane-bound NADH-ferredoxin oxidoreductase driven by an electrochemical Na(+)-gradient. This enzyme is related to the Rnf proteins involved in Rhodobacter capsulatus nitrogen fixation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acidaminococcus / enzymology
  • Acidaminococcus / metabolism
  • Acyl Coenzyme A / metabolism*
  • Amino Acids / metabolism*
  • Bacteria, Anaerobic / enzymology
  • Bacteria, Anaerobic / metabolism*
  • Clostridium / enzymology
  • Clostridium / metabolism
  • Fermentation
  • Ferredoxin-NADP Reductase / metabolism
  • Fusobacterium nucleatum / enzymology
  • Fusobacterium nucleatum / metabolism
  • Hydro-Lyases / metabolism
  • Nitrogenase / metabolism
  • Rhodobacter capsulatus / enzymology
  • Rhodobacter capsulatus / metabolism
  • Thauera / enzymology
  • Thauera / metabolism

Substances

  • Acyl Coenzyme A
  • Amino Acids
  • lactoyl-coenzyme A
  • Ferredoxin-NADP Reductase
  • Nitrogenase
  • 2-hydroxyglutaryl-CoA dehydratase
  • Hydro-Lyases
  • phenyllactate dehydratase