Expression of Pyridoxal 5'-Phosphate-Independent Racemases Can Reduce 2-Aminoacrylate Stress in Salmonella enterica.

The RidA protein (PF01042) from 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. , RidA homologs from all domains of life deaminate 2AA, and RidA proteins from plants, bacteria, yeast, and humans complement the mutant phenotype of a mutant strain of In the present study, a methanogenic archaeon, S2, was used to probe alternative mechanisms to restore metabolic balance. MMP0739, which is annotated as an aspartate/glutamate racemase, complemented a mutant strain and reduced the intracellular 2AA burden. The aspartate/glutamate racemase YgeA from or , when provided in , similarly restored wild-type growth to a 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. 2-Aminoacrylate is an endogenously generated reactive metabolite that can damage cellular enzymes if not directly quenched by the conserved deaminase RidA. This study used an archaeon to identify a RidA-independent mechanism to prevent metabolic stress caused by 2AA. The data suggest that a gene product annotated as an aspartate/glutamate racemase (MMP0739) produces a metabolite that can quench 2AA, expanding our understanding of strategies available to quench reactive metabolites.