Abstract
UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is an essential cytosolic enzyme in the biosynthesis of peptidoglycan. It becomes a potential bacterial target for screening promising antibacterial compounds as it is associated with the early phases of peptidoglycan production. MurA enzyme is conserved and necessary for bacterial viability with no mammalian homolog, which is a well-proven therapeutic research target. The present study reports the natural compounds from Boswellia serrata targeting the MurA enzyme. The identified inhibitors against MurA Escherichia coli (E. coli): β-boswellic acid (IC50 33.65 µM), Acetyl-β-boswellic acid (IC50 30.17 µM), and Acetyl-11-keto-β-boswellic acid (IC50 37.67 µM). Inhibitors showed a fourfold decrease in IC50 values on pre-incubation with substrate—UDP-N-acetyl-glucosamine (UDP-GlcNAc). Mode-of-inhibition studies revealed their uncompetitive nature with both the substrates. Although these boswellic acids have been explored for their pharmacological potential, this is the first study reporting these compounds' E. coli MurA inhibiting potential.
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Abbreviations
- E. coli :
-
Escherichia coli
- MurA:
-
UDP-N-Acetylglucosamine enolpyruvyl transferase
- UDP-GlcNAc:
-
UDP-N-acetyl-glucosamine
- ESBL :
-
Extended-spectrum beta-lactamase
- PEP:
-
Phosphoenol-pyruvate
- PG:
-
Peptidoglycan
- BA-:
-
Boswellic acid
- PMSF:
-
Phenylmethylsulphonyl fluoride
- IPTG:
-
Isopropyl-d-1-thiogalactopyranoside
- SDS-PAGE:
-
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
- MQ water:
-
Milli Q water
- IC50 :
-
Half-maximal inhibitory concentration
- MIC:
-
Minimum inhibitory concentration
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Acknowledgements
Authors are thankful to Director, Indian Institute of Integrative Medicine, Jammu for continuous support and encouragement. DR acknowledges the ICMR for SRF. The article bears Institutional Publication No. CSIR-IIIM/IPR/00390.
Funding
DR received a Senior Research Fellowship from the Indian Council of Medical Research, New Delhi, India (OMI-Fellowship/7/2020-ECD-I). This work was supported by Department of Health Research (DHR), New Delhi India (Grant no.GAP-2128).
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DR performed the major experiments and wrote the manuscript. FGK contributed in the molecular biology studies. HT performed the docking studies of the hits. PLS contributed in the synthesis of the compounds. AN guided the in-silico studies. VK contributed to the biological section and assisted with the final draft preparation. IAK conceptualized the whole manuscript as the corresponding author and edited the draft. SS analyzed the data, improved the MS and supervised the current study as the corresponding author and submitted the manuscript.
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Raina, D., Khan, F.G., Tiwari, H. et al. Boswellic acids, as novel inhibitor targeting peptidoglycan biosynthetic enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) in Escherichia coli. Arch Microbiol 204, 472 (2022). https://doi.org/10.1007/s00203-022-03066-7
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DOI: https://doi.org/10.1007/s00203-022-03066-7