UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and NH3-dependent NAD(+) synthetase (NadE) (MurB/NadE)

Lactobacillus reuteri MurB and NadE are essential bacterial enzymes that facilitate critical steps in cell wall synthesis and energy metabolism, respectively. MurB (UDP-N-acetylenolpyruvoylglucosamine reductase) is a flavoprotein that catalyzes the NADPH-dependent reduction of UDP-GlcNAc-enolpyruvate to UDP-MurNAc, a fundamental precursor for peptidoglycan biosynthesis (UniProt: Q13S65; PubMed: 11585509). NadE (NH3-dependent NAD(+) synthetase) is responsible for the final step of NAD+ biosynthesis, an indispensable cofactor for cellular respiration, redox balance, and DNA repair (UniProt: Q13S64; PubMed: 15103634). While these enzymes are traditional targets for antibiotic development in pathogenic bacteria, their presence in the probiotic species Lactobacillus reuteri makes them significant in the context of microbiome health and the unintended effects of broad-spectrum antimicrobials (PubMed: 25690661). Inhibition of these targets leads to the cessation of bacterial growth and eventual cell death due to structural instability and metabolic failure. Current research into MurB and NadE inhibitors, such as thiazolidinones and adenosine analogs, often utilizes these enzymes to evaluate the potential for unintended suppression of beneficial gut flora (PubChem; PubMed: 19451284).

Other names

MurBNadEUDP-N-acetylenolpyruvoylglucosamine reductaseNAD(+) synthetaseLactobacillus reuteri MurBLactobacillus reuteri NadEEnolpyruvyl-UDP-GlcNAc reductase

Inhibition of MurB prevents the formation of UDP-MurNAc, halting peptidoglycan assembly and leading to cell lysis. Inhibition of NadE prevents the synthesis of NAD+, disrupting essential redox reactions and energy metabolism, ultimately resulting in bacterial growth arrest.