Expression of pyridoxal 5'-phosphate-independent racemases can reduce 2-aminoacrylate stress in Salmonella enterica

Abstract

The RidA protein (PF01042) from Salmonella enterica is a deaminase that quenches 2-aminoacrylate (2AA) and other reactive metabolites. In the absence of RidA, 2AA accumulates, damages cellular enzymes, and compromises the metabolic network. In vitro, RidA homologs from all domains of life deaminate 2AA, and RidA proteins from plants, bacteria, yeast, and humans complement the mutant phenotype of a ridA mutant strain of S. enterica. In the present study, a methanogenic archaeon, Methanococcus maripaludis S2, was used to probe alternative mechanisms to restore metabolic balance. M. maripaludis MMP0739, which is annotated as an aspartate/ glutamate racemase, complemented a ridA mutant strain and reduced the intracellular 2AA burden. The aspartate/glutamate racemase YgeA from Escherichia coli or S. enterica, when provided in trans, similarly restored wild-type growth to a ridA mutant. These results uncovered a new mechanism to ameliorate metabolic stress, and they suggest that direct quenching by RidA is not the only strategy to quench 2AA.