Identification and Molecular Characterization of Genes Coding Pharmaceutically Important Enzymes from Halo-Thermo Tolerant Bacillus

Safary, Azam; Moniri, Rezvan; Hamzeh‐Mivehroud, Maryam; Dastmalchi, Siavoush

doi:10.15171/apb.2016.069

Cited by 13 publications

(4 citation statements)

References 62 publications

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“…[14][15][16] Among different types of NSs, the greater affinity, specificity, and functionality of enzymes to selectively target the desired cells/tissues make them prominent treatment modalities for a variety of diseases. [17][18][19][20] Bovine pancreatic ribonuclease A (RNase A, EC:3.1.27.5) is one of the best characterized small proteins (13.7 kDa), which was investigated for therapeutical purposes as a potential anticancer modality in 1972. 21 RNases represent a new class of cytotoxic and non-mutagenic enzymes, that can inhibit the proliferation of cancer cells through the catalytic cleavage of phosphodiester bonds in various types of single-stranded RNA (e.g., tRNA, rRNA, mRNA, and non-coding RNA), and hence, influence several signaling pathways, as well as protein biosynthesis at transcription and translation stages.…”

Section: Synthesis Of Peg Ligands Sh-peg-coohmentioning

confidence: 99%

PEGylated gold nanoparticles-ribonuclease induced oxidative stress and apoptosis in colorectal cancer cells

et al. 2019

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Introduction: Currently, drug-induced reactive oxygen species (ROS) mediating apoptosis pathway have extensively been investigated in designing effective strategies for colorectal cancer (CRC) chemotherapy. Bovine pancreatic ribonuclease A (RNase A) represents a new class of cytotoxic and non-mutagenic enzymes, and has gained more attention as a potential anticancer modality; however, the cytosolic ribonuclease inhibitors (RIs) restrict the clinical application of this enzyme. Nowadays, nanotechnology-based diagnostic and therapeutic systems have provided potential solutions for cancer treatments. Methods: In this study, the gold nanoparticles (AuNPs) were synthesized, stabilized by polyethylene glycol (PEG), functionalized, and covalently conjugated with RNase A. The physicochemical properties of engineered nanobiomedicine (AuNPs-PEG-RNase A) were characterized by scanning electron microscope (SEM), dynamic light scattering (DLS), and UV-vis spectrum. Then, its biological impacts including cell viability, apoptosis, and ROS production were evaluated in the SW-480 cells. Results: The engineered nanobiomedicine, AuNPs-PEG-RNase A, was found to effectively induce apoptosis in SW-480 cells and result in a significant reduction in cancer cell viability. Besides, the maximum production of ROS was obtained after the treatment of cells with an IC50 dose of AuNPs-PEG-RNase A. Conclusion: Based on the efficient ROS-responsiveness and the anticancer activity of RNase A of the engineered nanomedicine, this nanoscaled biologics may be considered as a potential candidate for the treatment of CRC.

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Section: Synthesis Of Peg Ligands Sh-peg-coohmentioning

confidence: 99%

PEGylated gold nanoparticles-ribonuclease induced oxidative stress and apoptosis in colorectal cancer cells

et al. 2019

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“…SL-1, isolated from Saline Lake of Iran 16 was investigated as the source of novel L-asparaginases. 19 Two ansA1 and ansA3 L-asparaginase genes from Bacillus sp. SL-1 were cloned and overexpressed in Origami(modified E. coli expression strain trxB2/gor2 double mutant) and E. coli BL21.…”

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confidence: 99%

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

et al. 2018

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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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“…However, some problems of Aps such as less circulating half-life, renal filtration due to small size, and fast degradation by nucleases have to be solved before clinical applications. 41 In order to establish a targeting approach and to accomplish the aforementioned goal, bio-conjugation of nanoparticles (NPs) loaded with therapeutic agents by using mAb (Fig. 1) or their analogs have been considered both in-vivo and in-vitro.…”

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Recent advances in targeted therapy of colorectal cancer: impacts of monoclonal antibodies nanoconjugates

2019

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Despite rapid advances in diagnostic and treatment approaches, the overall survival rate of cancer has not been improved. Colorectal cancer (CRC) is recognized as the third leading cause of neoplasm-related deaths worldwide, in large part due to its considerable metastasis and drug resistance. For developing new anticancer strategies, rapid progression of multimodal nanomedicines and nanoconjugates has provided promising treatment modalities for effective therapy of cancer. The limitations of cancer chemotherapy might be overcome through the use of such nanosized therapeutics, including nanoconjugates of monoclonal antibodies (mAbs) along with drugs and organic/inorganic nanoparticles. CRC cells express various molecular markers against which mAbs can be designed and used as targeting/therapeutic agents. This editorial highlights the importance of such targeted nanosystems against CRC.

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Identification and Molecular Characterization of Genes Coding Pharmaceutically Important Enzymes from Halo-Thermo Tolerant Bacillus

Cited by 13 publications

References 62 publications

PEGylated gold nanoparticles-ribonuclease induced oxidative stress and apoptosis in colorectal cancer cells

PEGylated gold nanoparticles-ribonuclease induced oxidative stress and apoptosis in colorectal cancer cells

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

Recent advances in targeted therapy of colorectal cancer: impacts of monoclonal antibodies nanoconjugates

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