Recent Strategies and Applications for l-Asparaginase Confinement

Abstract

l-asparaginase (ASNase, EC 3.5.1.1) is an aminohydrolase enzyme with important uses in the therapeutic/pharmaceutical and food industries. Its main applications are as an anticancer drug, mostly for acute lymphoblastic leukaemia (ALL) treatment, and in acrylamide reduction when starch-rich foods are cooked at temperatures above 100 °C. Its use as a biosensor for asparagine in both industries has also been reported. However, there are certain challenges associated with ASNase applications. Depending on the ASNase source, the major challenges of its pharmaceutical application are the hypersensitivity reactions that it causes in ALL patients and its short half-life and fast plasma clearance in the blood system by native proteases. In addition, ASNase is generally unstable and it is a thermolabile enzyme, which also hinders its application in the food sector. These drawbacks have been overcome by the ASNase confinement in different (nano)materials through distinct techniques, such as physical adsorption, covalent attachment and entrapment. Overall, this review describes the most recent strategies reported for ASNase confinement in numerous (nano)materials, highlighting its improved properties, especially specificity, half-life enhancement and thermal and operational stability improvement, allowing its reuse, increased proteolysis resistance and immunogenicity elimination. The most recent applications of confined ASNase in nanomaterials are reviewed for the first time, simultaneously providing prospects in the described fields of application.

Acrylamide in Bakery Products: A Review on Health Risks, Legal Regulations and Strategies to Reduce Its Formation

“…Numerous microorganisms may be valuable sources of asparaginase such as Aspergillus tamarii, Photobacterium spp., Aerobacter spp., Bacillus spp., Xanthomonas spp., Serratia spp., Proteus vulgaris, Pseudomonas aeruginosa, Vibrio succinogenes and Streptomyces griseus, etc. For therapeutic purposes, asparaginase is purified especially from E. coli or Dickeya dadantii whereas as an enzyme used for addition to foodstuffs the main sources of asparaginase are Aspergillus oryzae and Aspergillus niger [94,95]. In June 2007, JECFA analyzed asparaginase from Aspergillus oryzae and concluded from the available data that this enzyme does not induce a toxic effect on human health, but regulations were needed for its application nationally and internationally (JECFA, 2007).…”

L-Asparaginase-Based Biosensors

“…On the other hand, by applying a covalent bond Encyclopedia 2021, 1 849 between the enzyme and the immobilization support, the enzyme leaching is avoided, allowing for the recovery and reuse of the support/enzyme. Nevertheless, in this last option, the enzyme's active center amino acids should not be involved in covalent bonding to guarantee high levels of enzyme activity, which is defined by the enzyme binding orientation [6,7].…”

“…Since the amino acid L-asparagine is not mainly responsible for the taste and appearance of the processed foods, the desired organoleptic characteristics are preserved [19]. Thus, ASNase is already used to lower the acrylamide dosage in several food products, such as potatoes, bread, french fries, coffee and biscuits [6].…”

“…ASNase-based biosensors are a promising and innovative technology that can be used both to detect and monitor the level of L-asparagine in blood serum samples of leukemic patients and in different food samples [6]. The methods currently used to detect L-asparagine are based on spectroscopy and chromatography techniques [20], whereas the biosensor operation mode is mostly based on colorimetric detection.…”

“…On the other hand, by applying a covalent bond between the enzyme and the immobilization support, the enzyme leaching is avoided, allowing for the recovery and reuse of the support/enzyme. Nevertheless, in this last option, the enzyme's active center amino acids should not be involved in covalent bonding to guarantee high levels of enzyme activity, which is defined by the enzyme binding orientation [6,7]. The enzyme L-asparaginase (E.C.3.5.1.1, ASNase) is a chemotherapeutic agent for the treatment of lymphoproliferative disorders, specifically acute lymphoblastic leukemia (ALL), lymphomas and natural killer cell tumors.…”