A Comprehensive Review on l-Asparaginase and Its Applications

Abstract

L-asparaginase (LA) catalyzes the degradation of asparagine, an essential amino acid for leukemic cells, into ammonia and aspartate. Owing to its ability to inhibit protein biosynthesis in lymphoblasts, LA is used to treat acute lymphoblastic leukemia (ALL). Different isozymes of this enzyme have been isolated from a wide range of organisms, including plants and terrestrial and marine microorganisms. Pieces of information about the three-dimensional structure of L-asparaginase from Escherichia coli and Erwinia sp. have identified residues that are essential for catalytic activity. This review catalogues the major sources of L-asparaginase, the methods of its production through the solid state (SSF) and submerged (SmF) fermentation, purification, and characterization as well as its biological roles. In the same breath, this article explores both the past and present applications of this important enzyme and discusses its future prospects.

Purification and Cytotoxicity of L-asparaginase from Streptomyces griseoluteus GDJ1

“…It was shown that nearly 15-20% of patients treated with L-asparaginase of E. coli develop hypersensitivity and toxicity to the drug. [31], [32], [33], [1]. …”

“…From the literature surveyed and reviewed L-asparaginase exhibited potent anti neoplastic and anti lymphomatic activity against tumors [1], [46], [29], [32], [40] This enzyme causes selective death of asparagines dependent tumor cells and also induces apoptosis in tumor cells [26]. It has been shown that the glutaminase activity affected the normal cell growth [40], [1]..…”

“…All enzymes are proteins composed of amino acids, (in some cases RNA molecules) that catalyse reaction involved in development and maintenance of cell and help in defense against diseases with great specificity [1]. Enzymes act on their targets with higher affinity and specificity and convert multiple target molecules to desired products.…”

“…A major potential application of therapeutic enzymes is in the treatment of cancer. Cancer is the most precarious disease in which abnormal cells proliferate rapidly without control and able to invade other tissues by lymph or blood systems [1] and can cause organ failure and death if untreated. Globally, in 2012 nearly 14.1 million new cancer cases and 8.2 million deaths were occurred due to cancer [3] and by 2030 the number is expected to increase to 21 million.…”

<b>Optimization of asparaginase production from <i>Zymomonas mobilis</i> by continuous fermentation

“…Besides its use in antitumor treatments, asparaginase is also employed in food technology to reduce the formation of acrylamide (a toxic carcinogenic compound) in fried and baked food (Kornbrust, Stringer, Lange, & Hendriksen, 2009;Zuo, Zhang, Jiang, & Mu, 2015;Kumar, Shimray, Indrani, & Manonmani, 2014;Batool, Makky, Jalal, & Yusoff, 2016 used to decrease the formation of acrylamide (Hendriksen, Kornbrust, Ostergaard, & Stringer, 2009). Asparaginase has been focused in the search for other microorganisms that produce the enzyme with low toxicity and low-cost raw materials in the fermentation process.…”