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Bioimpacts. 2019;9(1): 15-23.
doi: 10.15171/bi.2019.03
PMID: 30788256
PMCID: PMC6378094
Scopus ID: 85060439417
  Abstract View: 3008
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Original Research

Highly efficient novel recombinant L-asparaginase with no glutaminase activity from a new halo-thermotolerant Bacillus strain

Azam Safary 1 ORCID logo, Rezvan Moniri 2,3, Maryam Hamzeh-Mivehroud 4,5, Siavoush Dastmalchi 4,5,6*

1 Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran
3 Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
4 Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
5 School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
6 Faculty of Pharmacy, Near East University, POBOX:99138, Nicosia, North Cyprus, Mersin 10, Turkey
*Corresponding Author: *Corresponding author: Siavoush Dastmalchi, Email: , siavoush11@yahoo.com, Email: dastmalchi.s@tbzmed.ac.ir

Abstract

Introduction: The bacterial enzyme has gained more attention in therapeutic application because of the higher substrate specificity and longer half-life. L-asparaginase is an important enzyme with known antineoplastic effect against acute lymphoblastic leukemia (ALL).

Methods: Novel L-asparaginase genes were identified from a locally isolated halo-thermotolerant Bacillus strain and the recombinant enzymes were overexpressed in modified E. coli strains, OrigamiTM B and BL21. In addition, the biochemical properties of the purified enzymes were characterized, and the enzyme activity was evaluated at different temperatures, pH, and substrate concentrations.

Results: The concentration of pure soluble enzyme obtained from Origami strain was ~30 mg/L of bacterial culture, which indicates the significant improvement compared to L-asparaginase produced by E. coli BL21 strain. The catalytic activity assay on the identified L-asparaginases (ansA1 and ansA3 genes) from Bacillus sp. SL-1 demonstrated that only ansA1 gene codes an active and stable homologue (ASPase A1) with high substrate affinity toward L-asparagine. The Kcat and Km values for the purified ASPase A1 enzyme were 23.96s-1 and 10.66 µM, respectively. In addition, the recombinant ASPase A1 enzyme from Bacillus sp. SL-1 possessed higher specificity to L-asparagine than L-glutamine. The ASPase A1 enzyme was highly thermostable and resistant to the wide range of pH 4.5–10.

Conclusion: The biochemical properties of the novel ASPase A1 derived from Bacillus sp. SL-l indicated a great potential for the identified enzyme in pharmaceutical and industrial applications.

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Submitted: 04 Aug 2018
Revision: 03 Sep 2018
Accepted: 05 Sep 2018
ePublished: 13 Sep 2018
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