Exploring EGY Type II L-Asparaginase Variant of Unique Glutaminase Activity: Cloning, Expression, Biochemical Characterization, and Molecular Docking Analysis

Hennigan JN, Lynch MD (2022) The past, present, and future of enzyme-based therapies. Drug Discovery Today 27(1):117–133. https://doi.org/10.1016/j.drudis.2021.09.004

Article  CAS  PubMed  Google Scholar 

Shishparenok AN, Gladilina YA, Zhdanov DD (2023) Engineering and expression strategies for optimization of L-asparaginase development and production. Int J Mol Sci 24:15220. https://doi.org/10.3390/ijms242015220

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vimal A, Kumar A (2022) l-asparaginase: need for an expedition from an enzymatic molecule to antimicrobial drug. Int J Pept Res Ther 28:1–5. https://doi.org/10.1007/s10989-021-10312-x

Article  CAS  Google Scholar 

Douer D, Gökbuget N, Stock W, Boissel N (2022) Optimizing use of L-asparaginase-based treatment of adults with acute lymphoblastic leukemia. Blood Rev 53:100908. https://doi.org/10.1016/j.blre.2021.100908

Article  CAS  PubMed  Google Scholar 

Song P, Ye L, Fan J, Li Y, Zeng X, Wang Z, Wang S, Zhang G, Yang P, Cao Z, Ju D (2015) Asparaginase induces apoptosis and cytoprotective autophagy in chronic myeloid leukemia cells. Oncotarget 6(6):3861–3873. https://doi.org/10.18632/oncotarget.2869

Article  PubMed  PubMed Central  Google Scholar 

Watanabe A, Miyake K, Nordlund J, Syvänen AC, van der Weyden L, Honda H, Yamasaki N, Nagamachi A, Inaba T, Ikawa T, Urayama KY, Kiyokawa N, Ohara A, Kimura S, Kubota Y, Takita J, Goto H, Sakaguchi K, Minegishi M, Iwamoto S, Inukai T (2022) Association of aberrant ASNS imprinting with asparaginase sensitivity and chromosomal abnormality in childhood BCP-ALL. Blood 136:2319–2333. https://doi.org/10.1182/blood.2019004090

Article  CAS  Google Scholar 

Nguyen HA, Su Y, Zhang JY, Antanasijevic A, Caffrey M, Schalk AM, Liu L, Rondelli D, Oh A, Mahmud DL, Bosland MC, Kajdacsy-Balla A, Peirs S, Lammens T, Mondelaers V, De Moerloose B, Goossens S, Schlicht MJ, Kabirov KK, Lyubimov AV, Merrill BJ, Saunthararajah Y, Van Vlierberghe P, Lavie A (2018) A novel l-Asparaginase with low l-Glutaminase coactivity is highly efficacious against both T- and B-cell acute lymphoblastic leukemias in vivo. Cancer Res 78:1549–1560. https://doi.org/10.1158/0008-5472.CAN-17-2106

Article  CAS  PubMed  PubMed Central  Google Scholar 

Offman MN, Krol M, Patel N, Krishnan S, Liu J, Saha V, Bates PA (2011) Rational engineering of L-asparaginase reveals importance of dual activity for cancer cell toxicity. Blood, J Am Soc Hematol 117(5):1614–1621. https://doi.org/10.1182/blood-2010-07-298422

Article  CAS  Google Scholar 

Gholami N, Ebrahimipour GH, Yaghoubi Avini M (2022) A study of the optimization of anti-tumor L-Asparaginase production using bacillus subtilis isolated from the soil of east Azerbaijan province. J Microb Biol 11(44):1–12. https://doi.org/10.22108/bjm.2021.129050.1393

Article  Google Scholar 

Vachher M, Sen A, Kapila R, Nigam A (2021) Microbial therapeutic enzymes: a promising area of biopharmaceuticals. Curr Res Biotechnol 3:195–208. https://doi.org/10.1016/j.crbiot.2021.05.006

Article  CAS  Google Scholar 

Kar PP, Srivastava A (2018) Immuno-informatics analysis to identify novel vaccine candidates and design of a multi-epitope based vaccine candidate against theileria parasites. Front Immunol 9:2213. https://doi.org/10.3389/fimmu.2018.02213

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kaliamurthi S, Selvaraj G, Junaid M, Khan A, Gu K, Wei D-Q (2018) Cancer immunoinformatics: a promising era in the development of peptide vaccines for human papillomavirus-induced cervical cancer. Curr Pharm Des 24:3791–3817. https://doi.org/10.2174/1381612824666181106094133

Article  CAS  PubMed  Google Scholar 

Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1006/abio.1976.9999

Article  CAS  PubMed  Google Scholar 

Imada A, Igarasi S, Nakahama K, Isono M (1973) Asparaginase and glutaminase activities of micro-organisms. J Gen Microbiol 76:85–99. https://doi.org/10.1099/00221287-76-1-85

Article  CAS  PubMed  Google Scholar 

Gomes E, de Souza AR, Orjuela GL, Da Silva R, de Oliveira TB, Rodrigues A (2016) Applications and benefits of thermophilic microorganisms and their enzymes for industrial biotechnology. In: Schmoll M, Dattenböck C (eds) Gene expression systems in fungi: advancements and applications. Springer International Publishing, Cham, pp 459–492

Chapter  Google Scholar 

Blachier J, Cleret A, Guerin N, Gil C, Fanjat JM, Tavernier F, Vidault L, Gallix F, Rama N, Rossignol R, Piedrahita D (2023) L-asparaginase anti-tumor activity in pancreatic cancer is dependent on its glutaminase activity and resistance is mediated by glutamine synthetase. Experimental Cell Res 426(2):113568. https://doi.org/10.1016/j.yexcr.2023.113568

Article  CAS  Google Scholar 

Kuo MT, Chen HHW, Feun LG, Savaraj N (2021) Targeting the proline-glutamine-asparagine-arginine metabolic axis in amino acid starvation cancer therapy. Pharmaceuticals 14:72. https://doi.org/10.3390/ph14010072

Article  CAS  PubMed  PubMed Central  Google Scholar 

Choi YK, Park KG (2018) Targeting glutamine metabolism for cancer treatment. Biomol & Therapeutics 26:19–28. https://doi.org/10.4062/biomolther.2017.178

Article  CAS  Google Scholar 

Chan WK, Lorenzi PL, Anishkin A, Purwaha P, Rogers DM, Sukharev S, Rempe SB, Weinstein JN (2014) The glutaminase activity of L-asparaginase is not required for anticancer activity against ASNS-negative cells. Blood 123(23):3596–3606. https://doi.org/10.1182/blood-2013-10-535112

Article  CAS  PubMed  PubMed Central  Google Scholar 

Van Trimpont M, Schalk AM, Hofkens K, Peeters E, T’Sas S, Vandemeulebroecke K, Su Y, De Loera A, Garcia A, Chen H, Lammens T, Van Vlierberghe P, Goossens S, Lavie A (2025) A human-like glutaminase-free asparaginase is highly efficacious in ASNSlow leukemia and solid cancer mouse xenograft models. Cancer Lett 611:217404. https://doi.org/10.1016/j.canlet.2024.217404

Article  CAS  Google Scholar 

Tsegaye K, Tsehai BA, Getie B (2024) Desirable L-asparaginases for treating cancer and current research trends. Front Microbiol 15:1269282. https://doi.org/10.3389/fmicb.2024.1269282

Article  PubMed  PubMed Central  Google Scholar 

Das CA, Kumar VG, Dhas TS, Karthick V, Kumar CV (2023) Nanomaterials in anticancer applications and their mechanism of action-A review. Nanomed Nanotechnol Biol Med 47:102613. https://doi.org/10.1016/j.nano.2022.102613

Article  CAS  Google Scholar 

Loch JI, Jaskolski M (2021) Structural and biophysical aspects of l-asparaginases: a growing family with amazing diversity. IUCrJ 8:514–531. https://doi.org/10.1107/S2052252521006011

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zielezinski A, Loch JI, Karlowski WM, Jaskolski M (2022) Massive annotation of bacterial L-asparaginases reveals their puzzling distribution and frequent gene transfer events. Sci Rep 12:15797. https://doi.org/10.1038/s41598-022-19689-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nguyen HA, Su Y, Lavie A (2016) Structural insight into substrate selectivity of Erwinia chrysanthemi L-asparaginase. Biochemistry 55:1246–1253. https://doi.org/10.1021/acs.biochem.5b01351

Article  CAS  PubMed  Google Scholar 

Pieters R, Hunger SP, Boos J, Rizzari C, Silverman L, Baruchel A, Goekbuget N, Schrappe M, Pui CH (2011) L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer 117:238–249. https://doi.org/10.1002/cncr.25489

Article  CAS  PubMed  Google Scholar 

Rogers TH, Babensee JE (2010) Altered adherent leukocyte profile on biomaterials in Toll-like receptor 4 deficient mice. Biomaterials 31:594–601. https://doi.org/10.1016/j.biomaterials.2009.09.077

Article  CAS  PubMed  Google Scholar 

Lubkowski J, Wlodawer A (2019) Geometric considerations support the double-displacement catalytic mechanism of l-asparaginase, protein science : a publication of the protein. Society 28:1850–1864. https://doi.org/10.1002/pro.3709

Article 

Comments (0)

No login
gif