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Critical Reviews in Oncology/hematology Dec 2017The purpose of this systematic review was to identify the available literature of the l-asparaginase producing fungi. This study followed the Preferred Reporting Items... (Review)
Review
The purpose of this systematic review was to identify the available literature of the l-asparaginase producing fungi. This study followed the Preferred Reporting Items for Systematic Reviews. The search was conducted on five databases: LILACS, PubMed, Science Direct, Scopus and Web of Science up until July 20th, 2016, with no time or language restrictions. The reference list of the included studies was crosschecked and a partial gray literature search was undertaken. The methodology of the selected studies was evaluated using GRADE. Asparaginase production, optimization using statistical design, purification and characterization were the main evaluated outcomes. Of the 1686 initially gathered studies, 19 met the inclusion criteria after a two-step selection process. Nine species of fungi were reported in the selected studies, out of which 13 studies optimized the medium composition using statistical design for enhanced asparaginase production and six reported purification and characterization of the enzyme. The genera Aspergillus were identified as producers of asparaginase in both solid and submerged fermentation and l-asparagine was the amino acid most used as nitrogen source. This systematic review demonstrated that different fungi produce l-asparaginase, which possesses a potential in leukemia treatment. However, further investigations are required to confirm the promising effect of these fungal enzymes.
Topics: Asparaginase; Aspergillus; Cell Line, Tumor; Fermentation; Fungi; Humans; Neoplasms
PubMed: 29198332
DOI: 10.1016/j.critrevonc.2017.11.006 -
Biomeditsinskaia Khimiia Feb 2020L-asparaginase is extensively used in the treatment of acute lymphoblastic leukemia and several other lymphoproliferative diseases. In addition to its biomedical... (Review)
Review
L-asparaginase is extensively used in the treatment of acute lymphoblastic leukemia and several other lymphoproliferative diseases. In addition to its biomedical application, L-asparaginase is also of prospective use in food industry to reduce the formation of acrylamide, which is classified as probably neurotoxic and carcinogenic to human, and in biosensors for determination of L-asparagine level in medicine and food chemistry. The importance of L-asparaginases in different fields, disadvantages of commercial ferments, and the fact that they are widespread in nature stimuli the search for biobetter L-asparaginases from new producing microorganisms. In this regard, extremofile microorganisms exhibit unique physiological properties such as thermal stability, adaptability to extreme cold conditions, salt and pH tolerance and so provide one of the most valuable sources for novel L-asparaginases. The present review summarizes the recent results on studying the structural, functional, physicochemical and kinetic properties, stability of extremophilic L-asparaginases in comparison with their mesophilic homologues.
Topics: Asparaginase; Asparagine; Extremophiles
PubMed: 32420891
DOI: 10.18097/PBMC20206602105 -
Environmental Science and Pollution... Apr 2022The considerable effect of enzymes on human health draws great attention to enzyme-based drugs (therapeutic enzymes), in recent times. L-asparaginase (ASNase) is a...
The considerable effect of enzymes on human health draws great attention to enzyme-based drugs (therapeutic enzymes), in recent times. L-asparaginase (ASNase) is a well-known therapeutic enzyme. It has varied applications and is a single molecule for the treatment of multiple diseases. This study tries to extract asparaginase from soybean debris (agricultural wastes) as a cheap plant source and compare this with microbial asparaginase as an agent in cancer chemotherapy. The asparaginase was extracted and purified from soybean debris (plant asparaginase) and Pseudomonas aeruginosa (microbial asparaginase), then the physiochemical characters were determined for the two enzymes, and the anticancer activity of plant and microbial asparaginase was determined against gastric cancer (CLS-145), pancreatic cancer (AsPC-1), colon cancer (HCT116), esophagus cancer (KYSE-410), liver cancer (HepG2), breast cancer (MCF-7), and cervical cancer (HELLA). The results showed that plant asparaginase was superior to microbial asparaginase in its physiochemical characters. Plant asparaginase showed higher stability and activity under the conditions of changing either the temperature or the pH; also plant asparaginase has a higher affinity to the asparagine than the microbial asparaginase; besides, this plant asparaginase did not show activity with glutamine as a substrate. The plant asparaginase showed higher anticancer activity than that of microbial asparaginase against all studied cancer cell lines. The present study introduces as the first time a comparative study between the plant and microbial asparaginase which proves that soybean debris asparaginase can be more efficient and safe than that of the microbial asparaginase as an anticancer agent.
Topics: Antineoplastic Agents; Asparaginase; Asparagine; Humans; Pseudomonas aeruginosa
PubMed: 34978032
DOI: 10.1007/s11356-021-17925-1 -
Current Hematologic Malignancy Reports Jun 2021The incorporation of pegaspargase in chemotherapy regimens has significantly improved the prognosis of ALL in adults. However, pegaspargase use poses many challenges due... (Review)
Review
PURPOSE OF REVIEW
The incorporation of pegaspargase in chemotherapy regimens has significantly improved the prognosis of ALL in adults. However, pegaspargase use poses many challenges due to its unique toxicity profile. Here, we review pegaspargase's most clinically significant toxicities, and provide guidance for their prevention and management in order to avoid unnecessary drug discontinuation and achieve maximum clinical benefit.
RECENT FINDINGS
Clinically significant toxicities of pegaspargase include thrombosis, hypersensitivity and inactivation, hepatotoxicity, pancreatitis, and hypertriglyceridemia. The majority of these toxicities are temporary, nonfatal, and can be managed supportively without permanent pegaspargase discontinuation. Special attention should be paid to inactivation, which can lead to treatment failure, as well as pancreatitis, which necessitates complete cessation of asparaginase therapy. The question of how to best proceed in patients who cannot tolerate pegaspargase remains unanswered, and is an important area of future investigation. Pegaspargase is an essential component of the pediatric-inspired regimens that have improved survival in adult ALL. Although pegaspargase's toxicity profile is unique, it is also highly manageable and should not be a barrier to achieving maximum clinical benefit using this drug.
Topics: Antineoplastic Agents; Asparaginase; Clinical Decision-Making; Disease Management; Drug-Related Side Effects and Adverse Reactions; Humans; Polyethylene Glycols
PubMed: 33978914
DOI: 10.1007/s11899-021-00638-0 -
Cancer Chemotherapy and Pharmacology Mar 2017The benefits of asparaginase (ASNASE) in the treatment of ALL and NHL are indisputable and new ASNASE preparations are under clinical development to overcome limitations... (Review)
Review
PURPOSE
The benefits of asparaginase (ASNASE) in the treatment of ALL and NHL are indisputable and new ASNASE preparations are under clinical development to overcome limitations of the actual ASNASE therapy, especially immunogenicity. Apart from ALL and NHL further indications of ASNASE are preclinically and clinically evaluated.
METHODS
We reviewed ASNASE literature and especially focused on the mechanism of action, on biomarker, which determine ASNASE sensitivity and resistance, and on ASNASE pharmacodynamics in vivo.
RESULTS
More than 40 years after the clinical introduction of ASNASE its mechanism of action is yet not fully understood. Studies on asparagine synthetase (ASNS) as biomarker for ASNASE resistance are contradictory and complicated by methodological obstacles. The role of glutamine hydrolysis for ASNASE efficacy is still debated, other mechanisms are possibly not yet identified. In addition, individual pharmacokinetic/-dynamic relationships cannot be properly addressed because of methodological limitations.
CONCLUSION
More sophisticated preclinical models and suitable methods for monitoring of ASNASE pharmacodynamics are urgently needed (1) to understand the mechanism of action, (2) to establish valid biomarkers for ASNASE sensitivity and resistance, (3) to evaluate the pharmacokinetics/-dynamics of ASNASEs in individual patients, and (4) to compare the bioequivalence of clinically established, as well as new ASNASE preparations.
Topics: Animals; Antineoplastic Agents; Asparaginase; Humans; Lymphoma, Non-Hodgkin; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 28197753
DOI: 10.1007/s00280-016-3236-y -
Andes Pediatrica : Revista Chilena de... Aug 2021
Topics: Asparaginase; Drug Hypersensitivity; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 34652385
DOI: 10.32641/andespediatr.v92i4.3825 -
Critical Reviews in Oncology/hematology Apr 2016L-Asparaginase (EC3.5.1.1) is an enzyme, which is used for treatment of acute lymphoblastic leukaemia (ALL) and other related blood cancers from a long time. This enzyme... (Review)
Review
L-Asparaginase (EC3.5.1.1) is an enzyme, which is used for treatment of acute lymphoblastic leukaemia (ALL) and other related blood cancers from a long time. This enzyme selectively hydrolyzes the extracellular amino acid L-asparagine into L-aspartate and ammonia, leading to nutritional deficiencies, protein synthesis inhibition, and ultimately death of lymphoblastic cells by apoptosis. Currently, bacterial asparaginases are used for treatment purpose but offers scepticism due to a number of toxicities, including thrombosis, pancreatitis, hyperglycemia, and hepatotoxicity. Resistance towards bacterial asparaginase is another major disadvantage during cancer management. This situation attracted attention of researchers towards alternative sources of L-asparaginase, including plants and fungi. Present article discusses about potential of L-asparaginase as an anticancer agent, its mechanism of action, and adverse effects related to current asparaginase formulations. This article also provides an outlook for recent developments in L-asparaginase discovery from alternative sources and their potential as a less toxic alternative to current formulations.
Topics: Antineoplastic Agents; Asparaginase; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 25630663
DOI: 10.1016/j.critrevonc.2015.01.002 -
Archives of Microbiology Jul 2020L-asparaginase (E.C.3.5.1.1) is an important enzyme that has been purified and characterized for over decades to study and evaluate its anti-carcinogenic activity... (Review)
Review
L-asparaginase (E.C.3.5.1.1) is an important enzyme that has been purified and characterized for over decades to study and evaluate its anti-carcinogenic activity against different lymphoproliferative disorders such as acute lymphoblastic leukemia (ALL) and Hodgkin's lymphoma. The ability of the enzyme to convert L-asparagine into aspartic acid and ammonia is the reason behind its anti-cancerous activity. Apart from its medicinal uses, it is widely used in food industry to tackle acrylamide, a probable human carcinogen and, production in carbohydrate-rich foods cooked at high temperatures. There are variety of organisms including microorganisms such as bacteria, fungi, algae, and plants that produce L-asparaginase. The enzyme obtained from different microbial and plant sources have different physiochemical properties and kinetic parameters. L-asparaginases have an optimum pH range between 6 and 10 and an optimum temperature between 37 and 85 °C. This article has reviewed the lowest molecular mass for L-asparaginase in Yersinia pseudotuberculosis Q66CJ2 which is 36.27 kDa, while the highest for Pseudomonas otitidis which has a molecular mass of 205 ± 3 kDa. This review is an attempt to summarize most of the available sources, their phylogenetic relationships, purification methods, data regarding different physiochemical and kinetic properties of L-asparaginase.
Topics: Ammonia; Asparaginase; Asparagine; Aspartic Acid; Bacteria; Fungi; Hodgkin Disease; Humans; Phylogeny; Plants; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 32052094
DOI: 10.1007/s00203-020-01814-1 -
Engineering and Expression Strategies for Optimization of L-Asparaginase Development and Production.International Journal of Molecular... Oct 2023Genetic engineering for heterologous expression has advanced in recent years. Model systems such as , and are often used as host microorganisms for the enzymatic... (Review)
Review
Genetic engineering for heterologous expression has advanced in recent years. Model systems such as , and are often used as host microorganisms for the enzymatic production of L-asparaginase, an enzyme widely used in the clinic for the treatment of leukemia and in bakeries for the reduction of acrylamide. Newly developed recombinant L-asparaginase (L-ASNase) may have a low affinity for asparagine, reduced catalytic activity, low stability, and increased glutaminase activity or immunogenicity. Some successful commercial preparations of L-ASNase are now available. Therefore, obtaining novel L-ASNases with improved properties suitable for food or clinical applications remains a challenge. The combination of rational design and/or directed evolution and heterologous expression has been used to create enzymes with desired characteristics. Computer design, combined with other methods, could make it possible to generate mutant libraries of novel L-ASNases without costly and time-consuming efforts. In this review, we summarize the strategies and approaches for obtaining and developing L-ASNase with improved properties.
Topics: Humans; Asparaginase; Asparagine; Leukemia; Escherichia coli; Models, Biological; Antineoplastic Agents
PubMed: 37894901
DOI: 10.3390/ijms242015220 -
Applied Microbiology and Biotechnology Feb 2015L-Asparaginases (EC 3.5.1.1) are enzymes that catalyze the hydrolysis of L-asparagine to L-aspartic acid and found in a variety of organisms from microorganisms to... (Review)
Review
L-Asparaginases (EC 3.5.1.1) are enzymes that catalyze the hydrolysis of L-asparagine to L-aspartic acid and found in a variety of organisms from microorganisms to mammals. However, they are mainly expressed and produced by microorganisms. Microbial L-asparaginases have received sustained attention due to their irreplaceable role in the therapy of acute lymphoblastic leukemia and for their inhibition of acrylamide formation during food processing. In this article, we review the application of microbial L-asparaginases in medical treatments and acrylamide mitigation. In addition, we describe in detail recent advances in the existing sources, purification, production, properties, molecular modification, and immobilization of L-asparaginase.
Topics: Acrylamide; Asparaginase; Asparagine; Aspartic Acid; Bacteria; Fungi; Humans; Hydrolysis; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 25492420
DOI: 10.1007/s00253-014-6271-9