The protein carboxymethyltransferase–dependent aspartate salvage pathway plays a crucial role in the intricate metabolic network of Escherichia coli

Abstract

Protein carboxymethyltransferase (Pcm) is a highly evolutionarily conserved enzyme that initiates the conversion of abnormal isoaspartate to aspartate residues. While it is commonly believed that Pcm facilitates the repair of damaged proteins, a number of observations suggest that it may have another role in cell functioning. We investigated whether Pcm provides a means for Escherichia coli to recycle aspartate, which is essential for protein synthesis and other cellular processes. We showed that Pcm is required for the energy production, the maintenance of cellular redox potential and of S-adenosylmethionine synthesis, which are critical for the proper functioning of many metabolic pathways. Pcm contributes to the full growth capacity both under aerobic and anaerobic conditions. Last, we showed that Pcm enhances the robustness of bacteria when exposed to sublethal antibiotic treatments and improves their fitness in the mammalian urinary tract. We propose that Pcm plays a crucial role in E. coli metabolism by ensuring a steady supply of aspartate.