Increased Activity of Cystathionine β-Lyase Suppresses 2-Aminoacrylate Stress in Salmonella enterica

J Bacteriol. 2018 Apr 9;200(9):e00040-18. doi: 10.1128/JB.00040-18. Print 2018 May 1.


Reactive enamine stress caused by intracellular 2-aminoacrylate accumulation leads to pleiotropic growth defects in a variety of organisms. Members of the well-conserved RidA/YER057c/UK114 protein family prevent enamine stress by enhancing the breakdown of 2-aminoacrylate to pyruvate. In Salmonella enterica, disruption of RidA allows 2-aminoacrylate to accumulate and to inactivate a variety of pyridoxal 5'-phosphate-dependent enzymes by generating covalent bonds with the enzyme and/or cofactor. This study was initiated to identify mechanisms that can overcome 2-aminoacrylate stress in the absence of RidA. Multicopy suppressor analysis revealed that overproduction of the methionine biosynthesis enzyme cystathionine β-lyase (MetC) (EC alleviated the pleiotropic consequences of 2-aminoacrylate stress in a ridA mutant strain. Degradation of cystathionine by MetC was not required for suppression of ridA phenotypes. The data support a model in which MetC acts on a noncystathionine substrate to generate a metabolite that reduces 2-aminoacrylate levels, representing a nonenzymatic mechanism of 2-aminoacrylate depletion.IMPORTANCE RidA proteins are broadly conserved and have been demonstrated to deaminate 2-aminoacrylate and other enamines. 2-Aminoacrylate is generated as an obligatory intermediate in several pyridoxal 5'-phosphate-dependent reactions; if it accumulates, it damages cellular enzymes. This study identified a novel mechanism to eliminate 2-aminoacrylate stress that required the overproduction, but not the canonical activity, of cystathionine β-lyase. The data suggest that a metabolite-metabolite interaction is responsible for quenching 2-aminoacrylate, and they emphasize the need for emerging technologies to probe metabolism in vivo.

Keywords: 2-aminoacrylate; RidA; cystathionine β-lyase; endogenous stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acrylates / metabolism*
  • Aminohydrolases / genetics
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cystathionine / metabolism
  • Lyases / genetics
  • Lyases / metabolism*
  • Methionine / biosynthesis
  • Mutation
  • Salmonella enterica / enzymology*
  • Salmonella enterica / genetics


  • Acrylates
  • Bacterial Proteins
  • Cystathionine
  • Methionine
  • Aminohydrolases
  • Lyases
  • cystathionine beta-lyase