Diverse origins of microbial L-asparaginases and their current miscellaneous applications

Document Type : Review Article

Authors

1 Department of Microbiology and Immunology, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University, Cairo, Egypt

2 Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, African Union Organization St., Abbassia 11566, Cairo, Egypt

3 Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University

Abstract

L-asparaginase, also known as amidohydrolase, catalyzes the breakdown of asparagine into aspartic acid and ammonia. Due to its ability to inhibit the biosynthesis of protein lymphoblasts, it is used to treat acute lymphoblastic leukemia (ALL). It also has other applications in the food industry by preventing the formation of acrylamide. Different organisms including bacteria, fungi, actinomycetes, and plants produce L-asparaginase. This review highlights different applications of L-asparaginase in the industrial fields, the major sources of L-asparaginase, its immunological reactions and production techniques through the solid state (SSF) and submerged (SmF) fermentation as well as optimization of the production process.

Keywords


1. Nigam PS. Microbial enzymes with special characteristics for biotechnological applications. Biomolecules. 2013; 3(3):597-611.
 
2. Periasamy Anbu, Subash CB Gopinath, Arzu Coleri Cihan, Bidur Prasad Chaulagain. Microbial enzymes and their applications in industries and medicine. Biomed Res int. 2013; 2013:1-13.
 
3. Anbu P, S.C.B. Gopinath, A.C. Cihan, B.P. Chaulagain. Strategies to characterize fungal lipases for applications in medicine and dairy industry. Biomed Res int. 2013:1-2.
 
4. Sinha R, Singh HR, Jha SK. Microbial L-asparaginase: present and future prospective. Int J Innov Res Sci Eng. 2013; 2(11):7031-51.
 
5. Bansal S, Srivastava A, Mukherjee G, Pandey R, Verma AK, Mishra P, et al. Hyperthermophilic asparaginase mutants with enhanced substrate affinity and antineoplastic activity: structural insights on their mechanism of action. FASEB J. 2012; 26(3):1161-71.
 
6. Piatkowska-Jakubas B, Krawczyk-Kuliś M, Giebel S, Adamczyk-Cioch M, Czyz A, Lech ME, et al. Use of L-asparaginase in acute lymphoblastic leukemia: recommendations of the Polish Adult Leukemia Group. Pol Arch Med Wewn. 2008;118(11):664-9.
 
7. Krishnapura PR, Belur PD, Subramanya S. A critical review on properties and applications of microbial l-asparaginases. Crit Revi  Microbiol. 2016;42(5):720-37.
 
8. Batool T, Makky EA, Muna Jalal, Mashitah M Yusoff. A comprehensive review of L-asparaginase and its applications. Appl Biochem Biotechnol. 2016; 178(5):900-23.
 
9. Kumar J, S, Pasrija D, Sinha RK, Singh HR, Nigam VK, Vidyarthi AS. Microbial L-asparaginase: a review on current scenario and future prospects. Int J  Pharm Sci and Res. 2012; 3(9):3076-90.
 
10. Souza PM, de Freitas MM, Cardoso SL, Pessoa A, Guerra ENS, Magalhães PO. Optimization and purification of l-asparaginase from fungi: A systematic review. Crit Rev Oncol Hematol. 2017;120:194-202.
 
11. Prager MD, Bachynsky N. Asparagine synthetase in asparaginase resistant and susceptible mouse lymphomas. Biochem Biophys Res Comm. 1968; 31(1):43-7.
 
12. Boos J. Use of l-asparaginase in childhood ALL. Crit Rev  Oncol Hematol. 1998; 2(28):97-113.
 
13. Ohnuma T, Bergel F, Bray R. Enzymes in cancer: asparaginase from chicken liver. Biochem J. 1967; 103(1):238.
 
14. Richards NG, Kilberg MS. Asparagine synthetase chemotherapy. Annu Rev Biochem. 2006; 75:629-54.
 
15. Ueno T, Ohtawa K, Mitsui K, Kodera Y, Hiroto M, Matsushima A. Cell cycle arrest and apoptosis of leukemia cells induced by L-asparaginase. Leukemia. 1997; 11(11):1858.
 
16. Asthana N, Azmi W. Microbial L-asparaginase: A potent antitumor enzyme. ind J Biotechnol. 2003;2:184-94.
 
17. Mottram DS, Wedzicha BL, Dodson AT. Food chemistry: acrylamide is formed in the Maillard reaction. Nature. 2002; 419(6906):448.
 
18. Pedreschi F, Mariotti MS, Granby K. Current issues in dietary acrylamide: formation, mitigation, and risk assessment. J  Sci  Food Agric. 2014;94(1):9-20.
 
19. Yu LL, Wang S, Sun B-G. Food safety chemistry: toxicant occurrence, analysis, and mitigation: CRC press; 2014.
 
20. Xu F, Oruna-Concha M-J, Elmore JS. The use of asparaginase to reduce acrylamide levels in cooked food. Food Chem. 2016; 210:163-71.
 
21. Sadd PA, Hamlet CG, Liang L. Effectiveness of methods for reducing acrylamide in bakery products. J agric food chem. 2008; 56(15):6154-61.
 
22. Bartkiene E, Jakobsone I, Juodeikiene G, Vidmantiene D, Pugajeva I, Bartkevics V. Study on the reduction of acrylamide in mixed rye bread by fermentation with bacteriocin-like inhibitory substances producing lactic acid bacteria in combination with Aspergillus niger glucoamylase. Food Control. 2013; 30(1):35-40.
 
23. Bartkiene E, Jakobsone I, Juodeikiene G, Vidmantiene D, Pugajeva I, Bartkevics V. Effect of lactic acid fermentation of lupine wholemeal on acrylamide content and quality characteristics of wheat-lupine bread. Int j  food sci  nutr. 2013; 64(7):890-6.
 
24. Kamkar A, Qajarbeygi P, Jannat B, Haj Hosseini Babaei A, Misaghi A, Molaee Aghaee E. The inhibitory role of autolyzed yeast of Saccharomyces cerevisiae, vitamins B3 and B6 on acrylamide formation in potato chips. Toxin Rev. 2015; 34(1):1-5.
 
25. Boegl p, Zuzana C, Eugen K. Impact of L-asparaginase on acrylamide content in potato products. J  Food  Nutr Res. 2006;45(4):141-6.
 
26. Parker JK, Balagiannis DP, Higley J, Smith G, Wedzicha BL, Mottram DS. Kinetic model for the formation of acrylamide during the finish-frying of commercial French fries. J  Agr  Food Chem. 2012;60(36):9321-31.
 
27. Zyzak DV, Sanders RA, Stojanovic M, Tallmadge DH, Eberhart BL, Ewald DK, et al. Acrylamide formation mechanism in heated foods. J Agr Food Chem. 2003; 51(16):4782-7.
 
28. Vass M, Amrein T, Schonbachler B, Escher F, Amado R. Ways to reduce the acrylamide formation in cracker products. Czech J Food Sci. 2004;22(I):19.
 
29. Verma N, Kumar K, Kaur G, Anand S. E. coli K-12 asparaginase-based asparagine biosensor for leukemia. Artif Cells Blood Substit Biotechnol. 2007; 35(4):449-56.
 
30. Verma N, Bansal M, Kumar S. Whole cell based miniaturized fiber optic biosensor to monitor L-asparagine. Adv Appl Sci Res. 2012; 3(2):809-14.
 
31. Borek D, Jaskólski M. Sequence analysis of enzymes with asparaginase activity. Acta Biochim Pol. 2001; 48:893-902.
 
32. Bruneau L, Chapman R, Marsolais F. Co-occurrence of both L-asparaginase subtypes in Arabidopsis: At3g16150 encodes a K+-dependent L-asparaginase. Planta. 2006; 224(3):668-79.
 
33. Abdel-Fattah YR, Olama ZA. L-asparaginase production by Pseudomonas aeruginosa in solid-state culture: evaluation and optimization of culture conditions using factorial designs. Process Biochem. 2002; 38(1):115-22.
 
34. Kumar S, Dasu VV, Pakshirajan K. Purification and characterization of glutaminase-free L-asparaginase from Pectobacterium carotovorum MTCC 1428. Bioresour Technol. 2011; 102(2):2077-82.
 
35. Izadpanah QF, Javadpour S, Malekzadeh K, Tamadoni Jahromi S, Rahimzadeh M. Persian gulf is a bioresource of potent L-asparaginase producing bacteria: Isolation & molecular differentiating. Int J Environ Res. 2014; 8(3):813-8.
 
36. Hymavathi M, Sathish T, Rao CS, Prakasham R. Enhancement of L-asparaginase production by isolated Bacillus circulans (MTCC 8574) using response surface methodology. Appl Biochem  Biotechnol. 2009; 159(1):191-8.
 
37. Prakasham R, Hymavathi M, Rao CS, Arepalli S, Rao JV, Kennady PK, et al. Evaluation of antineoplastic activity of extracellular asparaginase produced by isolated Bacillus circulans. Appl Biochem  Biotechnol. 2010; 160(1):72.
 
38. Joner PE. Purification and properties of l-asparaginase B from Acinetobacter calcoaceticus. Biochimica et Biophysica Acta (BBA)-Enzymology. 1976;438(1):287-95.
 
39. Mohapatra B, Sani R, Banerjee U. Characterization of L‐asparaginase from Bacillus sp. isolated from an intertidal marine alga (Sargassum sp.). Lett  Appl Microbiol. 1995; 21(6):380 3.
 
40. Rowly B, Wriston J. L-asparaginase from Serratia marcescens. Biochem  Biophys Res Commun. 1967; 28:160-71.
 
41. Shoshana B, Banks G, Skarstedt M, Fleming A, Bettelheim K, Connors T. The properties and large-scale production of L-asparaginase from Citrobacter. Microbiology. 1975; 91(1):1-16.
 
42. Nefelova M, Ignatov S, Chigalenchik A, Vinogradov B, Egorov N. Biosynthesis of L-asparaginase-2 by cultures of Bacillus polymyxa var. Ross. Prikladnaia biokhimiia i mikrobiologiia. 1978; 14(4):510-4.
 
43. Netrval J. Stimulation of L-asparaginase production in Escherichia coli by organic and amino acids. Folia microbiol. 1977;22(2):106-16.
 
44. Fisher SH, Wray LV. Bacillus subtilis 168 contains two differentially regulated genes encoding L-asparaginase. J  Bacteriol. 2002; 184(8):2148-54.
 
45. 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(2):180-4.
 
46. Golden KJ, Bernlohr RW. Nitrogen catabolite repression of the L-asparaginase of Bacillus licheniformis. J  Bacteriol. 1985; 164(2):938-40.
 
47. Sudhir AP, Dave BR, Prajapati AS, Panchal K, Patel D, Subramanian R. Characterization of a recombinant glutaminase-free l-asparaginase (ansa3) enzyme with high catalytic activity from Bacillus licheniformis. Appl Biochem  Biotechnol. 2014; 174(7):2504-15.
 
48. Mesas JM, Gil JA, Martín JF. Characterization and partial purification of L-asparaginase from Corynebacterium glutamicum. Microbiology. 1990; 136(3):515-9.
 
49. Maladkar N, Singh V, Naik S. Fermentative production and isolation of L-asparaginase from Erwinia carotovora, EC-113. Hindustan Antibiot bull. 1993; 35(1-2):77-86.
50. Moola ZB, Scawen M, Atkinson T, Nicholls D. Erwinia chrysanthemi L-asparaginase: epitope mapping and production of antigenically modified enzymes. Biochem J. 1994; 302(3):921-7.
 
51. Mikucki J, Szarapińska-Kwaszewska J, Krzemiński Z. Factors influencing L-asparaginase production by Staphylococci. Zentralbl Bakteriol Parasitenkd Infektionskr Hyg. 1977; 132(2):135-42.
 
52. Stark R, Suleiman M-S, Hassan I, Greenman J, Millar M. Amino acid utilisation and deamination of glutamine and asparagine by Helicobacter pylori. J Med Microbiol. 1997;46(9):793-800.
 
53. Rozalska M, Mikucki J. Staphylococcal L-asparaginase: catabolic repression of synthesis. Acta Microbiologica Polonica. 1992; 41(3-4):145-50.
 
54. Reddy K. Effect of C and N sources on asparaginase production by bacteria. Ind J Microbiol 1990;30(1):81-3.
 
55. Zhang N, Clarke F, Di Trapani G, Keough D, Beacham I. Guinea pig serum L-asparaginase: purification, and immunological relationship to liver L-asparaginase and serum L-asparaginases in other mammals. Comp Biochem Physiol B, Biochem Mol Biol. 1995; 112(4):607-12.
 
56. Shrivastava A, Khan AA, Shrivastav A, Jain SK, Singhal PK. Kinetic studies of L-asparaginase from Penicillium digitatum. Prep Biochem  Biotechnol. 2012; 42(6):574-81.
 
57. Gummadi C. Screening and isolation of novel glutaminase free L-asparaginase from fungal endophytes. Res J Microbiol. 2014; 9(4):163-76.
 
58. Saxena RK, Sinha U. L-asparaginase and glutaminase activities in the culture filtrates of Aspergillus nidulans. Curr sci. 1981; 50:218-9.
 
59. Mishra A. Production of L-asparaginase, an anticancer agent, from Aspergillus niger using agricultural waste in solid state fermentation. Appl Biochem  Biotechnol. 2006; 135(1):33-42.
 
60. Hendriksen HV, Kornbrust BA, Østergaard PR, Stringer MA. Evaluating the potential for enzymatic acrylamide mitigation in a range of food products using an asparaginase from Aspergillus oryzae. J  Agr  Food Chem. 2009; 57(10):4168-76.
 
61. Sarquis MIdM, Oliveira EMM, Santos AS, Costa GLd. Production of L-asparaginase by filamentous fungi. Mem Inst Oswaldo Cruz. 2004; 99(5):489-92.
 
62. Gurunathan B, Sahadevan R. Production of L-asparaginase from natural substrates by Aspergillus terreus MTCC 1782: Effect of substrate, supplementary nitrogen source and L-asparagine. Int J Chem React Eng. 2009;7(1):doi.org/10.2202/1542-6580.2050.
 
63. Raha S, Roy S, Dey S, Chakrabarty S. Purification and properties of an L-asparaginase from Cylindrocarpon obtusisporum MB-10. Biochem Int. 1990; 21(6):987-1000.
 
64. Mohapatra B, Bapuji M, Banerjee U. Production and properties of L-asparaginase from Mucor species associated with a marine sponge (Spirastrella sp.). Cytobios. 1997; 92(370-371):165-73.
65. Nakahama K, Imada A, Igarasi S, Tubaki K. Formation of L-asparaginase by Fusarium species. Microbiology. 1973;75(2):269-73.
 
66. Sahu MK, Sivakumar K, Poorani E, Thangaradjou T, Kannan L. Studies on L-asparaginase enzyme of actinomycetes isolated from estuarine fishes. J Environ Biol. 2007; 28(2):465.
 
67. Narayana K, Kumar K, Vijayalakshmi M. L-asparaginase production by Streptomyces albidoflavus. Ind J Microbiol. 2008; 48(3):331-6.
 
68.Gupta N, Mishra S, Basak U. Occurrence of Streptomyces aurantiacus in mangroves of Bhitarkanika. Malays J Microbiol. 2007;3(2):7-14.
 
69. Mostafa S, Salama M. L-asparaginase-producing Streptomyces from the soil of Kuwait. Zentralbl Bakteriol Naturwiss. 1979; 134(4):325-34.
 
70. Dejong PJ. L-Asparaginase production by Streptomyces griseus. Appl Microbiol. 1972; 23(6):1163-4.
 
71. Amena S, Vishalakshi N, Prabhakar M, Dayanand A, Lingappa K. Production, purification and characterization of L-asparaginase from Streptomyces gulbargensis. Braz J Microbiol. 2010; 41(1):173-8.
 
72. Mostafa S. Activity of L-asparaginase in cells of Streptomyces karnatakensis. Zentralbl Bakteriol Naturwiss. 1979; 134(4):343-51.
 
73. Koshy A, Dhevendaran K, Georgekutty M, Natarajan P. L-asparaginase in Streptomyces plicatus isolated from the alimentary canal of the fish, Gerres filamentosus (Cuvier). J Mar Biotechnol. 1997; 5:181-5.
 
74. Kavitha A, Vijayalakshmi M. Optimization and Purifi cation of L-Asparaginase Produced by Streptomyces tendae TK-VL_333. Z Naturforsch C. 2010; 65(7-8):528-31.
 
75. Ramya L, Doble M, Rekha V, Pulicherla K. L-Asparaginase as potent anti-leukemic agent and its significance of having reduced glutaminase side activity for better treatment of acute lymphoblastic leukemia. Appl Biochem  Biotechnol. 2012;167(8):2144-59.
 
76. Aghaiypour K, Wlodawer A, Lubkowski J. Structural basis for the activity and substrate specificity of Erwinia chrysanthemi L-asparaginase. Biochemistry. 2001; 40(19):5655-64.
 
77. Swain AL, Jaskólski M, Housset D, Rao J, Wlodawer A. Crystal structure of Escherichia coli L-asparaginase, an enzyme used in cancer therapy. Proc Nat Acad Sci. 1993; 90(4):1474-8.
 
78. Lubkowski J, Dauter M, Aghaiypour K, Wlodawer A, Dauter Z. Atomic resolution structure of Erwinia chrysanthemi L-asparaginase. Acta Cryst D. 2003; 59(1):84-92.
 
79. Kozak M, Jaskólski M, Rohm K. Preliminary crystallographic studies of Y25F mutant of periplasmic Escherichia coli L-asparaginase. Acta Biochim Pol. 2000;47(3):807-14.
 
80. Jaskolski M, Kozak M, Lubkowski J, Palm G, Wlodawer A. Structures of two highly homologous bacterial l‐asparaginases: a case of enantiomorphic space groups. Acta Cryst D. 2001; 57(3):369-77.
81. Sanches M, Barbosa JaAR, De Oliveira RT, Abrahão Neto J, Polikarpov I. Structural comparison of Escherichia coli L-asparaginase in two monoclinic space groups. Acta Cryst D. 2003; 59(3):416-22.
 
82. Ahlke E, Nowak‐Go¨ Ttl U, Schulze‐Westhoff P, Werber G, Bo¨ Rste H, WU¨ Rthwein G, et al. Dose reduction of asparaginase under pharmacokinetic and pharmacodynamic control during induction therapy in children with acute lymphoblastic leukemia. Brit J Haematol. 1997; 96(4):675-81.
 
83. Killander D, Dohlwitz A, Engstedt L, Franzen S, Gahrton G, Gullbring B, et al. Hypersensitive reactions and antibody formation during L‐asparaginase treatment of children and adults with acute leukemia. Cancer. 1976; 37(1):220-8.
 
84. Gurunathan B, Sahadevan R. Optimization of culture conditions and bench-scale production of L-asparaginase by submerged fermentation of Aspergillus terreus MTCC 1782. J Microbiol Biotechnol. 2012;22(7):923-9.
 
85. Lopes AM, Oliveira-Nascimento Ld, Ribeiro A, Tairum Jr CA, Breyer CA, Oliveira MAd, et al. Therapeutic l-asparaginase: upstream, downstream and beyond. Crit Rev  Biotechnol. 2017; 37(1):82-99.
 
86. Baskar G, Renganathan S. Evaluation and screening of nitrogen source for l-asparaginase production by Aspergillus terreus MTCC 1782 using latin square design. Res J  Math  Stat. 2009; 1(2):55-8.
 
87. Aida M, Farag, Sahar W, Hassan, Ehab A, Beltagy, Mohamed A, El-Shenawy. Optimization of production of anti-tumor l-asparaginase by free and immobilized marine Aspergillus terreus. Egypt J Aquat Res. 2015; 41(4):295-302.
 
88. Kiranmayi MU, Poda S, Vijayalakshmi M. Production and optimization of L-asparaginase by an actinobacterium isolated from Nizampatnam mangrove ecosystem. J Environ Biol. 2014;35(5):799.
 
89. Tippani R, Sivadevuni G. Nutritional factors effecting the production of L-asparaginase by the Fusarium sp. Afr J Biotechnol. 2012; 11(15):3692-6.
 
90. Vijayalakshmi M, Kavitha K, Akilandeswari K. Production of bioactive enzyme L-asparaginase from fungal isolates of water sample through submerged fermentation. Int JPharm Pharm Sci. 2012; 4(4):363-6.
 
91. Varalakshmi V, Raju JK. Optimization of l-asparaginase production by Aspergillus terreus mtcc 1782 using bajra seed flour under solid state fermentation. Int J Res Eng Technol. 2013; 2(09):121-9.
 
92. Hosamani R, Kaliwal B. L-asparaginase an anti-tumor agent production by Fusarium equiseti using solid state fermentation. Int J Drug Discov. 2011;3(2):88-99.
 
93. Nagarethinam S, Naik AN, Udupa N, Rao VJ, Vanathi MB. Microbial L-Asparaginase and its future prospects. Asian J MedRes. 2012; 1(4):159-68.
 
94. Ahmad N, Pandit NP, Maheshwari SK. L-asparaginase gene-a therapeutic approach towards drugs for cancer cell. Int J Biosci. 2012; 2(4):1-11.
95. Moorthy V, Ramalingam A, Sumantha A, Shankaranaya RT. Production, purification, and characterization of extracellular L-asparaginase from a soil isolate of Bacillus sp. Afr J Microbiol Res. 2010; 4(18):1862-7.
 
96. Mishra A, Das MD. Effect of pH on simultaneous saccharification and isomerization by glucoamylase and glucose isomerase. Appl Biochem Biotechnol. 2002; 102(1-6):193-9.
 
97. Mukherjee P, Pandey A, Selvakumar P, Ashakumary L, Gurusamy P. X-ray diffraction studies on solid state fermentation for the production of glucoamylase using Aspergillus niger NCIM 1248. J Sci Ind Res. 1998; 57(10-11):583-6.
 
98. Deokar VD, Vetal MD, Lambert Rodrigues. Production of intracellular L-asparaginase from Erwinia carotovora and its statistical optimization using response surface methodology (RSM). Int J Chem Sci. 2010; 1:25-36.
 
99. Sunitha M, Ellaiah P, Devi RB. Screening and optimization of nutrients for L-asparaginase production by Bacillus cereus MNTG-7 in SmF by plackett-burmann design. Afr JMicrobiol Res. 2010; 4(4):297-303.
 
100. El-Bessoumy AA, Sarhan M, Mansour J. Production, isolation, and purification of L-asparaginase from Pseudomonas aeruginosa 50071 using solid-state fermentation. BMB Reports. 2004; 37(4):387-93.
 
101. Cachumba JJM, Antunes FAF, Peres GFD, Brumano LP, Dos Santos JC, Da Silva SS. Current applications and different approaches for microbial l-asparaginase production. Braz J Microbiol. 2016;47:77-85.
 
102. Uygun M, Jurado-Sánchez B, Uygun DA, Singh VV, Zhang L, Wang J. Ultrasound-propelled nanowire motors enhance asparaginase enzymatic activity against cancer cells. Nanoscale. 2017; 9(46):18423-9.