Marine microbial L-asparaginase: Biochemistry, molecular approaches and applications in tumor therapy and in food industry

Qeshmi, Fatemeh Izadpanah; Homaei, Ahmad; Fernandes, Pedro; Javadpour, Sedigheh

doi:10.1016/j.micres.2018.01.011

Cited by 105 publications

(37 citation statements)

References 114 publications

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“…Several ASNase producing microorganisms have already been described in the literature, such as Escherichia coli, Dickeya chrysanthemi (previously known as Erwinia chrysanthemi), Saccharomyces cerevisiae, Aspergillus sp., Serratia marcescens, Proteus vulgaris among others, and screening work continues to find new ones (Rowley and Wriston, 1967; Tosa et al, 1971; Costa et al, 2016; Doriya and Kumar, 2016; Vimal and Kumar, 2017; Qeshmi et al, 2018; Vala et al, 2018). However, as previously mentioned, only the enzymes from E. coli and D. chrysanthemi are produced on an industrial scale for pharmaceutical use (Merck, 2000; European Medicines Agency, 2015, 2016; Medicines Evaluation Board, 2015).…”

Section: L-asparaginase Manufacturing: Production Process and Purificmentioning

confidence: 99%

Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles

Brumano

Silva

Costa-Silva

et al. 2019

Front. Bioeng. Biotechnol.

143

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L-Asparaginase (ASNase) is a vital component of the first line treatment of acute lymphoblastic leukemia (ALL), an aggressive type of blood cancer expected to afflict over 53,000 people worldwide by 2020. More recently, ASNase has also been shown to have potential for preventing metastasis from solid tumors. The ASNase treatment is, however, characterized by a plethora of potential side effects, ranging from immune reactions to severe toxicity. Consequently, in accordance with Quality-by-Design (QbD) principles, ingenious new products tailored to minimize adverse reactions while increasing patient survival have been devised. In the following pages, the reader is invited for a brief discussion on the most recent developments in this field. Firstly, the review presents an outline of the recent improvements on the manufacturing and formulation processes, which can severely influence important aspects of the product quality profile, such as contamination, aggregation and enzymatic activity. Following, the most recent advances in protein engineering applied to the development of biobetter ASNases (i.e., with reduced glutaminase activity, proteolysis resistant and less immunogenic) using techniques such as site-directed mutagenesis, molecular dynamics, PEGylation, PASylation and bioconjugation are discussed. Afterwards, the attention is shifted toward nanomedicine including technologies such as encapsulation and immobilization, which aim at improving ASNase pharmacokinetics. Besides discussing the results of the most innovative and representative academic research, the review provides an overview of the products already available on the market or in the latest stages of development. With this, the review is intended to provide a solid background for the current product development and underpin the discussions on the target quality profile of future ASNase-based pharmaceuticals.

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Section: L-asparaginase Manufacturing: Production Process and Purificmentioning

confidence: 99%

Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles

Brumano

Silva

Costa-Silva

et al. 2019

Front. Bioeng. Biotechnol.

143

View full text Add to dashboard Cite

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“…Asparaginase producing bacteria that have been reported are E.coli, Streptomyces spp., Bacillus spp., Serratia spp., Pseudomonas aeruginosa, Vibrio spp., Aeromonas spp., and Mesoflavibacter zeaxanthinifaciens (Izadpanah et al, 2018;Kenari et al, 2011;Lee et al, 2016). Since asparaginase was used as therapy for ALL treatment, these asparaginase producing bacteria including from Caulobacter flavus could be used as an enzyme sources.…”

Section: Isolation and 16s Rrna Analysismentioning

confidence: 99%

Screening of Bacteria Producing Asparaginase Free of Glutaminase and Urease from Hot Springs in West Sulawesi

Setiawan

Larasati

2019

J Bio Bio Edu

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L-asparaginase catalyzes the hydrolysis of asparagine into ammonia and aspartate. It has been used in chemotherapy for patients with acute lymphoblastic leukemia. L-asparaginase presents in animal, plant and microorganism. Long-term application of this enzyme can induce neurotoxicity due to the affinity towards glutamine and urea. The aim of this research was to find new source of glutaminase and urease-free asparaginase from bacteria. Bacteria were isolated from hot springs located in West Sulawesi using R2A media. The identification was employed by amplifying 16S rRNA gene. Screening of asparaginase was conducted using asparagine as single source of Nitrogen. Out of 21 isolates, 76% were Gram-negatives from the genus of Pseudomonas, Acinetobacter, Bosea, Caulobacter, Sphingomonas and Novosphingobium, while the rest of them were Gram-positives from the genus of Mycobacterium, Brachybacterium, Rhodococcus, and Staphylococcus. Twelve isolates which showed asparaginase activity were Caulobacter flavus HS1YWS2 and HS1XWS3, Acinetobacter sp. HS2XWS5, HS2XWS6, HS2XWS8, HS2YWS11, HS2YWS12, HS2YWS13, HS2ZWS14, HS2ZWS15 and HS2ZWS16. Isolates HS1YWS2 and HS1XWS3 were free of glutaminase and urease and showed the highest activity. This study was the first report of asparaginase activity from Caulobacter flavus. This result can further be used to explore the ability of asparaginase free of glutaminase and urease to treat acute lymphoblastic leukemia.

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“…In this regard, fungal sources have been explored for their eukaryotic nature, as their similarity to humans at cellular level could reduce the unwanted immunological reactions [36,37]. Several reports [38][39][40][41] and comprehensive reviews [20, [42][43][44] have been published, revealing the potential of fungi as a feasible source of ASNase and presenting antitumor activity [45,46]. In addition to being eukaryotes, they can produce ASNase with reduced glutaminase activity [47,48].…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity assessment of fungal l-asparaginases: an in silico approach

et al. 2020

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Acute lymphoblastic leukemia is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The enzyme l-asparaginase isolated from Escherichia coli and Dickeya chrysanthemi is a key factor in multiple therapies against this disease. Regardless of their effectiveness, these formulations present well-known adverse effects, highlighting the immunogenicity and allergenicity they cause. Some strategies have been adopted in this regard, such as PEGylation and modification by bioengineering as well as the search for new non-bacterial microorganisms producing the enzyme. Fungi have been shown to be asparaginase producers with high antitumor activity; however, little is known about the immunological features of fungal asparaginase. In this work, we developed the first immunoinformatics study focused on revealing the antigenic determinants that contribute to the immunogenicity of nine asparaginases of filamentous fungi experimentally tested, and compared them with the enzyme from E. coli. We were able to predict that the fungal asparaginases evaluated have a high degree of immunogenicity, which is an important result to consider if the aim is to produce clinical l-asparaginase from a fungal source. Likewise, for the first time, a bioinformatics-based approach was used to predict the immunogenic and allergenic epitopes present in fungal asparaginases.

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Marine microbial L-asparaginase: Biochemistry, molecular approaches and applications in tumor therapy and in food industry

Cited by 105 publications

References 114 publications

Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles

Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles

Screening of Bacteria Producing Asparaginase Free of Glutaminase and Urease from Hot Springs in West Sulawesi

Immunogenicity assessment of fungal l-asparaginases: an in silico approach

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