Insights into the Microbial L-Asparaginases: from Production to Practical Applications

Abstract

L-asparaginase is a valuable protein therapeutic drug utilized for the treatment of leukemia and lymphomas. Administration of asparaginase leads to asparagine starvation causing inhibition of protein synthesis, growth, and proliferation of tumor cells. Besides its clinical significance, the enzyme also finds application in the food sector for mitigation of a cancer-causing agent acrylamide. The numerous applications ensue huge market demands and create a continued interest in the production of costeffective, more specific, less immunogenic and stable formulations which can cater both the clinical and food processing requirements. The current review article approaches the process parameters of submerged and solid-state fermentation strategies for the microbial production of the L-asparaginase from diverse sources, genetic engineering approaches used for the production of L-asparaginase enzyme and major applications in clinical and food sectors. The review also addresses the immunological issues associated with the L-asparaginase usage and the immobilization strategies, drug delivery systems employed to circumvent the toxicity complications are also discussed. The future prospects for microbial Lasparaginase production are discussed at the end of the review article.

Penetration into Cancer Cells via Clathrin-Dependent Mechanism Allows L-Asparaginase from Rhodospirillum rubrum to Inhibit Telomerase

“…Normal cells can synthesize L-asparagine for their growth through the enzyme asparagine synthetase. Neoplastic cells lack the ability to synthesize asparagine due to the absence or shortage of L-asparagine synthetase and are dependent on an exogenous supply of this amino acid from the bloodstream [ 1 ].…”

In Silico Design of a Chimeric Humanized L-asparaginase

“…However, both enzymes have the same functionality, which points to the existence of a common ancestor. Moreover, since they present the same enzymatic function, there are structural residues that must be conserved and be common not only in these enzymes but in all those that belong to the same family to conserve the function of degrading asparagine [38,50,51]. Since human L-asparaginases, unlike the E. coli-derived one, possess a KM value outside the micromolar range and are therefore not clinically relevant, they are not suitable substitutes for clinically used bacterial enzymes [40].…”

Overview of the structure, side effects, and activity assays of l-asparaginase as a therapy drug of acute lymphoblastic leukemia

“…65 Thus, the employment of longer half-life and more stable formulations avoiding multiple dosing can reduce the chance of activating hypersensitivity reactions. 66 The basic therapeutic strategy presently utilized to avoid severe side effects in patients is the employment of different sources of L-ASNase; therefore, many studies have been focused on identifying different sources of L-ASNase and evading the strong immunogenic…”