L-Asparaginase bioprospection from Bacillus species

Franciely da Costa Alves , Valnês da Silva Rodrigues-Junior , Samuel Paulo Cibulski

Systems Microbiology and Biomanufacturing ›› 2026, Vol. 6 ›› Issue (2) : 40

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Systems Microbiology and Biomanufacturing ›› 2026, Vol. 6 ›› Issue (2) :40 DOI: 10.1007/s43393-026-00433-z
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L-Asparaginase bioprospection from Bacillus species

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Abstract

L-Asparaginase (L-ASNase) is an enzyme widely used on protocols for the treatment of acute lymphoblastic leukemia (ALL) and some solid tumors. It works by depleting asparagine, an essential amino acid for the growth of neoplastic cells, while normal cells can synthesize it independently. Today, only L-ASNase isolated from Escherichia coli and Erwinia chrysanthemi is approved and commercially available for clinical use. However, its application is often limited due to adverse effects and the development of resistance. To circumvent these challenges, researchers are exploring new sources of L-ASNase, mainly in bacteria, aiming advantages, like greater stability, reduced immunogenicity and, improved pharmacokinetic properties. Recent studies have identified promising L-ASNase candidates from Bacillus genus. In this context, we review recent data on the isolation of novel L-ASNase from Bacillus species, highlighting the importance of bioprospection for improving oncologic therapies.

Keywords

Bacteria / Enzyme / Bioprospection / Cancer

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Franciely da Costa Alves, Valnês da Silva Rodrigues-Junior, Samuel Paulo Cibulski. L-Asparaginase bioprospection from Bacillus species. Systems Microbiology and Biomanufacturing, 2026, 6(2): 40 DOI:10.1007/s43393-026-00433-z

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References

[1]

Abdelrazek NA, Elkhatib WF, Raafat MM, Aboulwafa MM. Experimental and bioinformatics study for production of l-asparaginase from Bacillus licheniformis: a promising enzyme for medical application. AMB Express, 2019, 9: 1-16

[2]

Abdelrazek NA, Elkhatib WF, Raafat MM, Aboulwafa MM. Production, characterization and bioinformatics analysis of l-asparaginase from a new Stenotrophomonas maltophilia EMCC2297 soil isolate. AMB Express, 2020, 10: 1-16

[3]

Alrumman SA, Mostafa YS, Al-izran KAet al.. Production and Anticancer Activity of an L-asparaginase from Bacillus licheniformis isolated from the Red Sea, Saudi Arabia. Sci Rep, 2019, 9: 1-14

[4]

Arredondo-Nuñez A, Monteiro G, Flores-Fernández CNet al.. Characterization of a type II l-asparaginase from the halotolerant Bacillus subtilis CH11. Life, 2023, 13 2145

[5]

Ashok A, Doriya K, Rao JVet al.. Microbes producing L-Asparaginase free of glutaminase and urease isolated from extreme locations of Antarctic soil and moss. Sci Rep, 2019, 9 1423

[6]

Baluchi A, Homaei A. Immobilization of l-asparaginase on chitosan nanoparticles for the purpose of long-term application. Int J Biol Macromol, 2024, 257 128655

[7]

Baral A, Gorkhali R, Basnet Aet al.. Selection of the optimal L-asparaginase II against acute lymphoblastic leukemia: an in silico approach. Jmirx Med, 2021, 2 e29844

[8]

Baruchel A, Brown P, Rizzari Cet al.. Increasing completion of asparaginase treatment in childhood acute lymphoblastic leukaemia (ALL): summary of an expert panel discussion. ESMO Open, 2020

[9]

Belén LH, Lissabet JB, de Oliveira Rangel-Yagui Cet al.. A structural in silico analysis of the immunogenicity of l-asparaginase from Escherichia coli and Erwinia carotovora. Biologicals, 2019, 59: 47-55

[10]

Cecconello DK, de Magalhães MR, Werlang ICRet al.. Asparaginase: an old drug with new questions. Hematol Transfus Cell Ther, 2020, 42: 275-282

[11]

Cedar H, Schwartz JH. Production of l-Asparaginase II by Escherichia coli. J Bacteriol, 1968, 96: 2043-2048

[12]

Chand S, Mahajan RV, Prasad JPet al.. A comprehensive review on microbial <scp>l</scp> -asparaginase: Bioprocessing, characterization, and industrial applications. Biotechnol Appl Biochem, 2020, 67: 619-647

[13]

Chand S, Mihooliya KN, Sahoo DKet al.. L-asparaginase from Bacillus flexus strain SS: isolation, screening, production process optimization, purification, and anticancer activity. Appl Biochem Microbiol, 2022, 58: 416-427

[14]

Cirilo HNC, Feitosa AR, Silva GSda. Avaliação da eficácia e segurança de pegaspargase, em comparação à L-asparaginase, e sua viabilidade econômica no tratamento de leucemia linfoblástica aguda: Série temática: avaliação de tecnologias em saúde hospitalar (ATS-H). HU Rev, 2024, 49: 1-11

[15]

da Cunha MC, dos Santos Aguilar JG, de Melo RRet al.. Fungal L-asparaginase: strategies for production and food applications. Food Res Int, 2019, 126 108658

[16]

Davarpanah M, Bakhtiari R, Javadi A, Eshraghi SS. Manufacture of L-asparaginase by actinobacteria isolated from rhizosphere of plants in Tehran with strong anti-cancer activity. Egypt J Vet Sci, 2022, 53: 9-14

[17]

de Souza Silva ML, Melquiades DB, de Melo Morais ÍRet al.. L-asparaginase microbiana com potencial antioxidante. Conjecturas, 2022, 22: 548-562

[18]

Dumina M, Zhgun A, Pokrovskaya Met al.. A novel L-Asparaginase from hyperthermophilic Archaeon Thermococcus sibiricus: heterologous expression and characterization for biotechnology application. Int J Mol Sci, 2021, 22 9894

[19]

El-Fakharany E, Orabi H, Abdelkhalek E, Sidkey N. Purification and biotechnological applications of L-asparaginase from newly isolated Bacillus halotolerans OHEM18 as antitumor and antioxidant agent. J Biomol Struct Dyn, 2022, 40: 3837-3849

[20]

El-Gendy MMAA, Awad MF, El-Shenawy FS, El-Bondkly AMA. Production, purification, characterization, antioxidant and antiproliferative activities of extracellular L-asparaginase produced by Fusarium equiseti AHMF4. Saudi J Biol Sci, 2021, 28: 2540-2548

[21]

El-Naggar NEA, Hamouda RA, Elshafey N. Artificial intelligence-based optimization for extracellular L-glutaminase free L-asparaginase production by Streptomyces violaceoruber under solid state fermentation conditions. Sci Rep, 2024, 14 29625

[22]

Erva RR, Goswami AN, Suman Pet al.. Optimization of L-asparaginase production from novel Enterobacter sp., by submerged fermentation using response surface methodology. Prep Biochem Biotechnol, 2017, 47: 219-228

[23]

Ghattavi S, Homaei A. Marine enzymes: classification and application in various industries. Int J Biol Macromol, 2023, 230 123136

[24]

Gholami N, Ebrahimipour GH, Yaghoubi Avini M. A study of the optimization of anti-tumor l-asparaginase production using Bacillus subtilis isolated from the soil of East Azerbaijan Province. J Microbiol Biol, 2022, 11: 1-12

[25]

Ghosh S, Murthy S, Govindasamy S, Chandrasekaran M. Optimization of L-asparaginase production by Serratia marcescens (NCIM 2919) under solid state fermentation using coconut oil cake. Sustain Chem Process, 2013, 2013(1): 1-8

[26]

Hadi WAM, Edwin BT, Nair AJ. Isolation and identification of marine Bacillus altitudinis KB1 from coastal Kerala: asparaginase producer. J Mar Biol Assoc India, 2021, 63: 43-48

[27]

Hanada K, Kawada K, Obama K. Targeting asparagine metabolism in solid tumors. Nutrients, 2025, 17 179

[28]

Hasan EAI, El-Shahawy RM, Atalla Kh M, Abdelaleim YF. Optimization of conditions for L-asparaginase production by certain bacterial strains isolated from soil at Fayoum Governorate. Fayoum J Agric Res Dev, 2022, 36: 356-367

[29]

Iraninasab S, Homaei A, Mosaddegh E, Torkzadeh-Mahani M. Polyamidoamine dendrimers functionalized with ZnO-chitosan nanoparticles as an efficient surface for L-asparaginase immobilization. Appl Biochem Biotechnol, 2024, 196: 971-991

[30]

Izadpanah Qeshmi F, Homaei A, Khajeh Ket al.. Production of a novel marine Pseudomonas aeruginosa recombinant L-asparaginase: insight on the structure and biochemical characterization. Mar Biotechnol, 2022, 24: 599-613

[31]

Jana A, Biswas S, Ghosh R, Modak R. Recent advances in L-Asparaginase enzyme production and formulation development for acrylamide reduction during food processing. Food Chem X, 2025, 25 102055

[32]

Jia M, Xu M, He B, Rao Z. Cloning, expression, and characterization of L-asparaginase from a newly isolated Bacillus subtilis B11-06. J Agric Food Chem, 2013, 61: 9428-9434

[33]

Kuwabara T, Prihanto AA, Wakayama M, Takagi K. Purification and characterization of Pseudomonas aeruginosa PAO1 asparaginase. Procedia Environ Sci, 2015, 28: 72-77

[34]

Lailaja VP, Hari V, Sumithra TGet al.. In vitro and in silico analysis unravelled clinically desirable attributes of Bacillus altitudinis L-asparaginase. J Appl Microbiol, 2024, 135: LXAE062

[35]

Mathew DE, Soni A, Shinde PB, Mantri VA. A Potent drug l-asparaginase from marine origins: a comprehensive review. Mar Bioact Mol Biomed Pharmacother Appl, 2023

[36]

Medeiros E, Cavalcante F, Silva V, et al. Diversidade Cultural de Cepas de Actinobactérias do Semiárido. Enci Bio 2018;15:205-218. https://doi.org/10.18677/EnciBio_2018A87.

[37]

Modi T, Gervais D. Improved pharmacokinetic and pharmacodynamic profile of a novel PEGylated native Erwinia chrysanthemi L-Asparaginase. Invest New Drugs, 2022, 40: 21-29

[38]

Mostafa Y, Alrumman S, Alamri Set al.. Enhanced production of glutaminase-free l-asparaginase by marine Bacillus velezensis and cytotoxic activity against breast cancer cell lines. Electron J Biotechnol, 2019, 42: 6-15

[39]

Mousa M, El-Dein MMN, Abou-Dobara MI, Metwally NE Purification and immobilization of L-asparaginase from Citrobacter freundii EGY-NE1, 2021.https://doi.org/10.21203/RS.3.RS-876391/V1

[40]

Mukherjee J, Majumdar S, Scheper T. Studies on nutritional and oxygen requirements for production of L- asparaginase by Enterobacter aerogenes. Appl Microbiol Biotechnol, 2000, 53: 180-184

[41]

Muneer F, Siddique MH, Azeem Fet al.. Microbial l-asparaginase: purification, characterization and applications. Arch Microbiol, 2020, 202: 967-981

[42]

Nicholson WL, Munakata N, Horneck Get al.. Resistance of Bacillus endospores to extreme terrestrial and extraterrestrial environments. Microbiol Mol Biol Rev, 2000, 64: 548-572

[43]

Osman ME, Abo-Elnasr AA, Mohamed ET. Exploring bioactive potential of Streptomyces thinghirensis WAE1 from Wadi El-Natron, Egypt. Indian J Microbiol, 2024, 64: 1685-1696

[44]

Özdal M, Gülmez Ö, Gökçe E, Algur Ö. Purification and characterization of glutaminase and urease-free l-asparaginase from Bacillus atrophaeus with acrylamide reduction potential. Int J Biol Chem, 2024, 17: 13-22

[45]

Patel PG, Panseriya HZ, Vala AKet al.. Exploring current scenario and developments in the field of microbial L-asparaginase production and applications: a review. Process Biochem, 2022, 121: 529-541

[46]

Pokrovsky VS, Kazanov MD, Dyakov INet al.. Comparative immunogenicity and structural analysis of epitopes of different bacterial L-asparaginases. BMC Cancer, 2016, 16 89

[47]

Qeshmi FI, Homaei A, Fernandes P, Javadpour S. Marine microbial L-asparaginase: biochemistry, molecular approaches and applications in tumor therapy and in food industry. Microbiol Res, 2018, 208: 99-112

[48]

Radadiya A, Zhu W, Coricello Aet al.. Improving the treatment of acute lymphoblastic leukemia. Biochemistry, 2020, 59: 3193-3200

[49]

Raj JEEA, Baskaran Aet al.. Isolation and Screening of L-asparaginase and L-glutaminase producing bacteria and their antimicrobial potential from environmental sources. Article IOSR J Pharm Biol Sci, 2016, 11: 47-53

[50]

Ray M, Kundu P, Adhikari S, Pramanik N Microbial production of L-asparaginase by an isolated Bacillus paramycoides MRS4 strain and optimization of process parameters. Indian J Biotechnol. 2021;20:242-251.

[51]

Rodríguez-Vargas R, Villanueva-Flores F, Gutiérrez-Chávez MFet al.. Enzymatic properties of a L-asparaginase without secondary glutaminase activity from Streptomyces scabrisporus. PLoS ONE, 2025, 20 e0336433

[52]

Safary A, Moniri R, Hamzeh-Mivehroud M, Dastmalchi S. Highly efficient novel recombinant l-asparaginase with no glutaminase activity from a new halo-thermotolerant Bacillus strain. Bioimpacts, 2018, 9 15

[53]

Saleena SK, Johnson JI, Joseph JKet al.. Production and optimization of l-asparaginase by Streptomyces koyangensis SK4 isolated from Arctic sediment. J Basic Microbiol, 2023, 63: 417-426

[54]

Salzer W, Bostrom B, Messinger Yet al.. Asparaginase activity levels and monitoring in patients with acute lymphoblastic leukemia. Leuk Lymphoma, 2018, 59: 1797-1806

[55]

Schallmey M, Singh A, Ward OP. Developments in the use of Bacillus species for industrial production. Can J Microbiol, 2004, 50: 1-17

[56]

Schmidt MP, Ivanov AV, Coriu D, Miron IC. L-asparaginase toxicity in the treatment of children and adolescents with acute lymphoblastic leukemia. J Clin Med, 2021, 1019 4419

[57]

Shafqat I, Shahzad S, Yasmin Aet al.. Characterization and applications of glutaminase free L-asparaginase from indigenous Bacillus halotolerans ASN9. PLoS ONE, 2023, 18 e0288620

[58]

Shrivastava A, Khan AA, Khurshid Met al.. Recent developments in l-asparaginase discovery and its potential as anticancer agent. Crit Rev Oncol Hematol, 2016, 100: 1-10

[59]

Tsegaye K, Tsehai BA, Getie B. Desirable L-asparaginases for treating cancer and current research trends. Front Microbiol, 2024, 15: 1269282

[60]

Van Trimpont M, Peeters E, De Visser Yet al.. Novel insights on the use of L-asparaginase as an efficient and safe anti-cancer therapy. Cancers (Basel), 2022, 14 902

[61]

Vimal A, Kumar A. Biotechnological production and practical application of L-asparaginase enzyme. Biotechnol Genet Eng Rev, 2017, 33: 40-61

[62]

Wahab MRA, Palaniyandi T, Wyson Jet al.. Extracellular l-asparaginase synthesis Bacillus niacin isolation, optimization, and characterization from marine saltern sediment sources. Avicenna J Med Biotechnol, 2024, 16 40

[63]

Wakil SM, Adelegan AA. Screening, production and optimization of L-asparaginase from soil bacteria isolated in Ibadan, South-western Nigeria. J Basic Appl Sci, 2015, 11: 39-51

[64]

Wang Y, Xu W, Wu Het al.. Microbial production, molecular modification, and practical application of l-asparaginase: a review. Int J Biol Macromol, 2021, 186: 975-983

[65]

Warangkar SC, Khobragade CN. Purification, characterization, and effect of thiol compounds on activity of the erwinia carotovora L-asparaginase. Enzym Res, 2010

[66]

Yim S, Kim M. Purification and characterization of thermostable l-asparaginase from Bacillus amyloliquefaciens MKSE in Korean soybean paste. LWT, 2019, 109: 415-421

[67]

Yuan Q, Yin L, He Jet al.. Metabolism of asparagine in the physiological state and cancer. Cell Commun Signal, 2024, 22 163

[68]

Zhang S, Xie Y, Zhang Cet al.. Biochemical characterization of a novel l-asparaginase from Bacillus megaterium H-1 and its application in French fries. Food Res Int, 2015, 77: 527-533

[69]

Zhou R, Liang T, Li Tet al.. Possible mechanism of metabolic and drug resistance with L-asparaginase therapy in childhood leukaemia. Front Oncol, 2023

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