A thioredoxin-dependent peroxiredoxin Q from Corynebacterium glutamicum plays an important role in defense against oxidative stress

Abstract

Peroxiredoxin Q (PrxQ) that belonged to the cysteine-based peroxidases has long been identified in numerous bacteria, but the information on the physiological and biochemical functions of PrxQ remain largely lacking in Corynebacterium glutamicum. To better systematically understand PrxQ, we reported that PrxQ from model and important industrial organism C. glutamicum, encoded by the gene ncgl2403 annotated as a putative PrxQ, played important roles in adverse stress resistance. The lack of C. glutamicum prxQ gene resulted in enhanced cell sensitivity, increased ROS accumulation, and elevated protein carbonylation levels under adverse stress conditions. Accordingly, PrxQ-mediated resistance to adverse stresses mainly relied on the degradation of ROS. The physiological roles of PrxQ in resistance to adverse stresses were corroborated by its induced expression under adverse stresses, regulated directly by the stress-responsive ECF-sigma factor SigH. Through catalytical kinetic activity, heterodimer formation, and bacterial two-hybrid analysis, we proved that C. glutamicum PrxQ catalytically eliminated peroxides by exclusively receiving electrons from thioredoxin (Trx)/thioredoxin reductase (TrxR) system and had a broad range of oxidizing substrates, but a better efficiency for peroxynitrite and cumene hydroperoxide (CHP). Site-directed mutagenesis confirmed that the conserved Cys49 and Cys54 are the peroxide oxidation site and the resolving Cys residue, respectively. It was also discovered that C. glutamicum PrxQ mainly existed in monomer whether under its native state or functional state. Based on these results, a catalytic model of PrxQ is being proposed. Moreover, our result that C. glutamicum PrxQ can prevent the damaging effects of adverse stresses by acting as thioredoxin-dependent monomeric peroxidase could be further applied to improve the survival ability and robustness of the important bacterium during fermentation process.

A Novel Thioredoxin-Dependent Peroxiredoxin (TPx-Q) Plays an Important Role in Defense Against Oxidative Stress and Is a Possible Drug Target in Babesia microti

“…Afterwards, the generated TPx-Q is ready for another catalytic cycle. Su et al (30) indicated that the two cysteine residues are essential for enzymatic activity by mutation analysis. Furthermore, they proved that C. glutamicum TPx-Q catalytically eliminates peroxides by exclusively receiving electrons from Trx/TrxR system (30).…”

“…Su et al (30) indicated that the two cysteine residues are essential for enzymatic activity by mutation analysis. Furthermore, they proved that C. glutamicum TPx-Q catalytically eliminates peroxides by exclusively receiving electrons from Trx/TrxR system (30). Unlike the typical 2-Cys Prx proteins, TPx-Q may exist as monomers, dimers, or a mixture (52).…”

“…Molecular chaperones can assist the covalent folding of proteins and prevent the protein aggregation (57). Su et al (30) found that TPx-Q functions as molecular chaperone and peroxidase. Cho et al (58) first reported that Prx Q of Deinococcus radiodurans R1 is a monomeric atypical 2-Cys Prx and has dual activity as peroxidase and a molecular chaperone.…”

“…The TPx-Q proteins are thiol-based peroxidases, and are important for maintaining redox homeostasis in several organisms. TPx-Q is an atypical Prx that has already been identified in bacteria, parasites, and some lower eukaryotes but is not found in mammals (28)(29)(30)(31).…”

Thioredoxin and protein-disulfide isomerase selectivity for redox regulation of proteins in <i>Corynebacterium glutamicum</i>

“…These phenomena suggested important functions of Trxs and PDIs. Previously, trx1 and trxR1 were shown to play an important role in reducing mycothiol peroxidase (MPx)\thiol peroxidase (Prx)\ methionine sulfoxide reductase A (MsrA)\peroxiredoxin Q (PrxQ) in C. glutamicum (Si et al, 2015a;Si et al, 2017;Si et al, 2015b;Su et al, 2018).…”