Phylogenetic study of L-asparaginase II (AsnB) in the bacteria domain and fungi kingdom

L-asparaginase II (AsnB), an important enzyme in the pharmaceutical field, is often used in the treatment of acute lymphoblastic leukemia (ALL). Only AsnB from E.coli K۱۲ and Erwinia has been used as a chemotherap agent. Although these enzymes have been successfully used in treatment, several medical complications like severe immune responses leading to sensitivity, and anaphylaxis. have limited their use. Thus, there is a need to search for other sources of AsnB with novel therapeutic properties and rational design to reduce side effects. Thirty fulllength amino acid sequences of AsnBs from diverse bacteria and fungi were collected from the protein database of the National Center for Biotechnology Information. The multiple sequence alignment was performed through the MAFFT algorithm and curated by the BMGE method on the online server NGPhylogeny. The phylogenetic tree was created using the maximum likelihood method based on the Le Gascuel model by Mega-۷ software. The phylogenetic tree of AsnBs shows three distinct clusters of enzymes distributed in Gram-negative bacteria including therapeutic E.coli K۱۲ enzyme, Gram-positive bacteria, and a cluster consisting of B.subtilis sequences, fungi, and E.chrysantemi which indicates plausible horizontal gene transfer among these species in distance times. Due to the low bootstrap values, the exact position of the branches shows some uncertainty. Two FDA-approved AsnBs have di↵erent phylogenies. Although other asparaginases with anti-tumor properties are more related to E.coli; the enzyme resemblance of fungi and B.subtilis to Erwinia enzyme suggests that these microorganisms could serve as a suitable substitute. Also, The tree shows the divergence in the phylogeny of the Gram-positive group.Suggesting that this group’s asparaginase could serve as a suitable substitute for current drugs, as their immunogenicity may di↵er significantly from those of commercial enzymes. The potential of other AsnB of Gram-positive bacteria and fungi should be explored to obtain an enzyme with fewer side effects against (ALL).

کلیدواژه ها:

L-asparaginase II ، Acute lymphoblastic leukemia ، Phylogenetic analysis ، Immunogenicity