How an overlooked gene in coenzyme a synthesis solved an enzyme mechanism predicament

Research output: Contribution to journalReview articlepeer-review


Coenzyme A (CoA) is an essential cofactor throughout biology. The first committed step in the CoA synthetic pathway is synthesis of β-alanine from aspartate. In Escherichia coli and Salmonella enterica panD encodes the responsible enzyme, aspartate-1-decarboxylase, as a proenzyme. To become active, the E. coli and S. enterica PanD proenzymes must undergo an autocatalytic cleavage to form the pyruvyl cofactor that catalyzes decarboxylation. A problem was that the autocatalytic cleavage was too slow to support growth. A long-neglected gene (now called panZ) was belatedly found to encode the protein that increases autocatalytic cleavage of the PanD proenzyme to a physiologically relevant rate. PanZ must bind CoA or acetyl-CoA to interact with the PanD proenzyme and accelerate cleavage. The CoA/acetyl-CoA dependence has led to proposals that the PanD-PanZ CoA/acetyl-CoA interaction regulates CoA synthesis. Unfortunately, regulation of β-alanine synthesis is very weak or absent. However, the PanD-PanZ interaction provides an explanation for the toxicity of the CoA anti-metabolite, N5-pentyl pantothenamide.

Original languageEnglish (US)
Pages (from-to)687-694
Number of pages8
JournalMolecular Microbiology
Issue number6
StatePublished - Jun 2023


  • CoA
  • autocatalysis
  • pantothenate
  • pyruvyl cofactor
  • β-alanine

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology


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