The involvement of coenzyme A esters in the dehydration of (R)-phenyllactate to (E)-cinnamate by Clostridium sporogenes

Eur J Biochem. 2000 Jun;267(12):3874-84. doi: 10.1046/j.1432-1327.2000.01427.x.

Abstract

Phenyllactate dehydratase from Clostridium sporogenes grown anaerobically on L-phenylalanine catalyses the reversible syn-dehydration of (R)-phenyllactate to (E)-cinnamate. Purification yielded a heterotrimeric enzyme complex (130 +/- 15 kDa) composed of FldA (46 kDa), FldB (43 kDa) and FldC (40 kDa). By re-chromatography on Q-Sepharose, the major part of FldA could be separated and identified as oxygen insensitive cinnamoyl-CoA:phenyllactate CoA-transferase, whereas the transferase depleted trimeric complex retained oxygen sensitive phenyllactate dehydratase activity and contained about one [4Fe-4S] cluster. The dehydratase activity required 10 microM FAD, 0.4 mM ATP, 2.5 mM MgCl2, 0.1 mM NADH, 5 microM cinnamoyl-CoA and small amounts of cell-free extract (10 microg protein per mL) similar to that known for 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans. The N-terminus of the homogenous FldA (39 amino acids) is homologous to that of CaiB (39% sequence identity) involved in carnitine metabolism in Escherichia coli. Both enzymes are members of an emerging group of CoA-transferases which exhibit high substrate specificity but apparently do not form enzyme CoA-ester intermediates. It is concluded that dehydration of (R)-phenyllactate to (E)-cinnamate proceeds in two steps, a CoA-transfer from cinnamoyl-CoA to phenyllactate, catalysed by FldA, followed by the dehydration of phenyllactyl-CoA, catalysed by FldB and FldC, whereby the noncovalently bound prosthetic group cinnamoyl-CoA is regenerated. This demonstrates the necessity of a 2-hydroxyacyl-CoA intermediate in the dehydration of 2-hydroxyacids. The transient CoA-ester formation during the dehydration of phenyllactate resembles that during citrate cleavage catalysed by bacterial citrate lyase, which contain a derivative of acetyl-CoA covalently bound to an acyl-carrier-protein (ACP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / metabolism
  • Amino Acid Sequence
  • Cell-Free System
  • Cinnamates / metabolism*
  • Clostridium / genetics
  • Clostridium / metabolism*
  • Coenzyme A / metabolism*
  • Enzymes / isolation & purification
  • Esters / metabolism
  • Fermentation
  • Hydro-Lyases / isolation & purification
  • Hydro-Lyases / metabolism
  • Lactates / metabolism*
  • Molecular Sequence Data
  • NAD / metabolism
  • Operon
  • Phenylpropionates / metabolism

Substances

  • Acyl Coenzyme A
  • Cinnamates
  • Enzymes
  • Esters
  • Lactates
  • Phenylpropionates
  • NAD
  • 3-phenyllactic acid
  • 3-phenylpropionic acid
  • cinnamoyl-coenzyme A
  • Hydro-Lyases
  • phenyllactate dehydratase
  • Coenzyme A