L-asparaginases of extremophilic microorganisms in biomedicine

Abstract

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.

A Novel L-Asparaginase from Hyperthermophilic Archaeon Thermococcus sibiricus: Heterologous Expression and Characterization for Biotechnology Application

“…As previously reported, the level of homology between L-ASNases of archaeal and nonarchaeal origin is rather low [ 43 , 54 ]. The identity of TsA and well-characterized mesophilic bacterial L-ASNases from Pectobacterium atrosepticum ( Erwinia carotovora subsp.…”

“…Regardless of the source, L-ASNases contain highly conserved amino acid residues, crucial for their catalytic activity [ 49 , 54 ]. In the case of L-ASNase II from E. coli (EcAII), widely used in oncohematology, these residues for the processed enzyme (native signal peptide cleaved) are Thr12, Tyr25, Ser58, Gln59, Thr89, Asp90, Lys162 and Glu283 ( Figure 1 b).…”

“…and shares a low level of sequence identity with mesophilic L-ASNases. Available crystallographic data of L-ASNases of various origins indicate that, despite the low degree of homology, which may not exceed 20–30%, they have conserved regions that determine the similarity of their tertiary structures and the catalytic mechanism [ 49 , 54 , 59 , 64 ]. According to the amino acid sequence alignments, TsA displayed eight conserved residues ( Figure 1 b) essential for the catalytic activity, namely Thr12, Tyr22, Ser55, Thr56, Thr86, Asp87, Lys157 and Glu279.…”

Heterologous Expression and Rational Design of l-asparaginase from Rhizomucor miehei to Improve Thermostability

“…l -asparaginase (EC 3.5.1.1) is an amide hydrolase that catalyzes the hydrolysis of l -asparagine to l -aspartic acid and ammonia [ 1 ]. This enzyme can be used to treat childhood acute leukemia and in the production of low-acrylamide foods [ 2 , 3 ]. In 1963, Broome [ 4 ] discovered l -asparaginase in guinea pig serum and attributed the antitumor properties of the latter reported by Kidd in 1953 [ 3 ] to this l -asparaginase activity.…”