Dihydrodipicolinate synthase is not inhibited by its substrate, (S)-aspartate beta-semialdehyde

Biochem J. 2004 Feb 1;377(Pt 3):757-62. doi: 10.1042/BJ20031389.


DHDPS (dihydrodipicolinate synthase; EC is the enzyme that catalyses the first unique step of lysine biosynthesis in plants and micro-organisms. As such, it has attracted much attention as a target for herbicide and anti-microbial action. DHDPS has two substrates: pyruvate and ( S )-aspartate beta-semialdehyde [( S )-ASA]. There are various literature reports that suggest that high levels of ( S )-ASA inhibit the enzyme [Karsten (1997) Biochemistry 36, 1730-1739; Stahly (1969) Biochim. Biophys. Acta 191, 439-451], whereas others have not observed this phenomenon. We have resolved this long-running literature debate and shown unequivocally that this difference in reported behaviour can be attributed to differences in the preparation of ( S )-ASA used by each researcher. DHDPS is not inhibited by its substrate; rather, the inhibition is due to an, as yet, unidentified inhibitor in preparations of the substrate generated by ozonolysis. Furthermore, we demonstrate that ( R )-ASA is neither an inhibitor nor a substrate of DHDPS from Escherichia coli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / chemical synthesis
  • Aspartic Acid / chemistry
  • Aspartic Acid / metabolism*
  • Dihydrodipicolinate Reductase
  • Enzyme Inhibitors / metabolism
  • Escherichia coli / enzymology
  • Escherichia coli Proteins / antagonists & inhibitors
  • Escherichia coli Proteins / metabolism
  • Hydro-Lyases / antagonists & inhibitors*
  • Hydro-Lyases / isolation & purification
  • Hydro-Lyases / metabolism*
  • Oxidoreductases Acting on CH-CH Group Donors / isolation & purification
  • Stereoisomerism
  • Substrate Specificity


  • Enzyme Inhibitors
  • Escherichia coli Proteins
  • Aspartic Acid
  • aspartic semialdehyde
  • Dihydrodipicolinate Reductase
  • Oxidoreductases Acting on CH-CH Group Donors
  • Hydro-Lyases
  • 4-hydroxy-tetrahydrodipicolinate synthase