RESEARCHERS at the Indian Institute of Technology Hyderabad (IITH), working with scientists from the National Centre for Polar and Ocean Research (NCPOR), Goa, have isolated Antarctic fungi that contain L-Asparaginase, an enzyme-based chemotherapeutic agent used to treat acute lymphoblastic leukemia (ALL). The isolation of L-Asparaginase containing fungi from extreme environments could lead to the development of new chemotherapeutic treatment methods that have fewer side effects than the existing methods.
ALL is the most common type of childhood cancer. In the disease, the bone marrow produces an excess of immature lymphocytes, a form of white blood cells. One of the most frequently used chemotherapy drugs to treat ALL is the enzyme L-Asparaginase. L-Asparaginase reduces the supply of asparagine, an amino acid that is essential for the synthesis of protein, to cancer cells. This prevents the growth and proliferation of the malignant cells. The work has recently been published in the Open Source Journal, Nature Scientific Reports.
The L-Asparaginase enzyme used for chemotherapy is currently derived from commonly found bacteria such as Escherichia coli and Erwinia chrysanthemi. These enzymes are always associated with two other enzymes, glutaminase and urease, both of which cause adverse side effects in patients such as pancreatitis, hemostasis abnormalities, central nervous system dysfunction and immunological reactions. “Extensive purification steps are necessary before L-Asparaginase derived from bacteria is used as a drug to treat ALL. This increases the cost of the drug,” said the principal investigator, D. Santhosh Kumar of IITH.
Seeking alternate sources of L-Asparaginase, the researchers screened and isolated fungi collected from the soil and mosses in Schirmacher Hills, Dronning Maud Land, Antarctica. These fungi were found to have L-Asparaginase free of glutaminase and urease. From 55 samples of fungi, 30 isolates had pure L-Asparaginase. Maximum enzymatic activity was seen in a strain of fungus called Trichosporon asahii IBBLA1 and the enzyme activity was comparable to that of purified enzymes obtained from bacterial sources.
The researchers stated: “Fungal species have the ability to mimic the properties of the human cells, as both are eukaryotic in nature, which makes it easier for their usage in treatment of ALL”.
Compiled by R. Ramachandran