Generic placeholder image

Recent Patents on Biotechnology

Editor-in-Chief

ISSN (Print): 1872-2083
ISSN (Online): 2212-4012

Mini-Review Article

Fibrinolytic Enzymes From Extremophilic Microorganisms in the Development of New Thrombolytic Therapies: Technological Prospecting

Author(s): James Romero Soares Bispo, Igor Gomes de Oliveira Lima, Maurício Bernardo da Silva, Alexya de Oliveira Feitosa, Ana Caroline Melo dos Santos, Magna Suzana Alexandre Moreira, Michel Rodrigo Zambrano Passarini, Paulo Eduardo Aguiar Saraiva Câmara, Luiz Henrique Rosa, Valéria Maia Oliveira, Aline Cavalcanti de Queiroz and Alysson Wagner Fernandes Duarte*

Volume 15, Issue 3, 2021

Published on: 05 August, 2021

Page: [169 - 183] Pages: 15

DOI: 10.2174/1872208315666210805154713

Price: $65

Abstract

Extremophilic microorganisms from a wide variety of extreme natural environments have been researched, and many biotechnological applications have been carried out, due to their capacity to produce biomolecules resistant to extreme conditions, such as fibrinolytic proteases. The search for new fibrinolytic enzymes is important in the development of new therapies against cardiovascular diseases. This article aimed to evaluate the patents filed about protease with fibrinolytic activity produced by extremophilic microorganisms whose use is aimed at the development of new drugs for the treatment of cardiovascular diseases. The prospecting was carried out using data on deposits and patent concessions made available on the technological bases: European Patent Office (EPO), United States Patent and Trademark Office (USPTO), World Intellectual Property Organization (WIPO), Instituto Nacional de Propriedade Industrial – Brazil (INPI), The LENS and Patent Inspiration. The International Patent Classification and subclasses and groups for each document were also evaluated. Although 382 patents were selected using terms related to extreme environments, such as “thermophile” and “acidophiles”, few were related to clinical use and were mainly performed using Bacillus subtilis and Streptomyces megasporus strains. A highlight of nattokinase was produced by Bacillus subtilis GDN and actinokinase by Streptomyces megasporus SD5. The low number of patents on enzymes with this profile (extreme environments) revealed a little-explored field, promising in the development of new microbial thrombolytic drugs, such as fibrinolytic enzymes with less adverse effects.

Keywords: Cardiovascular disease, fibrinolytic activity, innovation, pharmaceutical patents, thrombolytic drugs, technological bases.

Graphical Abstract

[1]
World health statistics 2019: Monitoring health for the SDGs, sustainable development goals. World Health Organization 2019; 31-5.
[2]
Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics-2021 update: A report from the American Heart Association. Circulation 2021; 143(8): e254-743.
[http://dx.doi.org/10.1161/CIR.0000000000000950] [PMID: 33501848]
[3]
Banerjee A, Chen S, Pasea L, et al. Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic. Euro J Prev Cardiol 2021.
[4]
Jerjes-Sánchez C. Thrombolysis in pulmonary embolism 2015; Springer: Heidelberg 2015; pp. 1-17.
[http://dx.doi.org/10.1007/978-3-319-19707-4_1]
[5]
Periayah MH, Halim AS, Mat Saad AZ. Mechanism action of platelets and crucial blood coagulation pathways in hemostasis. Int J Hematol Oncol Stem Cell Res 2017; 11(4): 319-27.
[PMID: 29340130]
[6]
Gale AJ. Continuing education course #2: Current understanding of hemostasis. Toxicol Pathol 2011; 39(1): 273-80.
[http://dx.doi.org/10.1177/0192623310389474] [PMID: 21119054]
[7]
Higazi AA-R. Fibrinolysis Overview. In: Laurent GJ, Shapiro SD, Eds. Encyclopedia of Respiratory Medicine. Academic Press: United States 2006; pp. 201-5.
[http://dx.doi.org/10.1016/B0-12-370879-6/00153-8]
[8]
Musso C, Pereira FEL. Circulation changes.Bogliolo, Pathology. 9th ed. Brazil: Guanabara Koogan 2016; pp. 93-160.
[9]
Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med 2008; 359(9): 938-49.
[http://dx.doi.org/10.1056/NEJMra0801082] [PMID: 18753650]
[10]
Kotzé RC, Ariëns RA, de Lange Z, Pieters M. CVD risk factors are related to plasma fibrin clot properties independent of total and or γ′ fibrinogen concentration. Thromb Res 2014; 134(5): 963-9.
[http://dx.doi.org/10.1016/j.thromres.2014.08.018] [PMID: 25213709]
[11]
Banerjee A, Chisti Y, Banerjee UC. Streptokinase-a clinically useful thrombolytic agent. Biotechnol Adv 2004; 22(4): 287-307.
[http://dx.doi.org/10.1016/j.biotechadv.2003.09.004] [PMID: 14697452]
[12]
Verma MK, Pulicherla KK. Lumbrokinase – A Potent and Stable Fibrin–Specific Plasminogen Activator. International Journal of Bio-Science and Bio-Technology 2011; 3(2): 57-70.
[13]
Kim JS, Kim JE, Choi BS, et al. Purification and characterization of fibrinolytic metalloprotease from Perenniporia fraxinea mycelia. Mycol Res 2008; 112(Pt 8): 990-8.
[http://dx.doi.org/10.1016/j.mycres.2008.01.029] [PMID: 18550350]
[14]
Deepak V, Ilangovan S, Sampathkumar MV, et al. Medium optimization and immobilization of purified fibrinolytic URAK from Bacillus cereus NK1 on PHB nanoparticles. Enzyme Microb Technol 2010; 47(6): 297-304.
[http://dx.doi.org/10.1016/j.enzmictec.2010.07.004]
[15]
Sanchez EF, Flores-Ortiz RJ, Alvarenga VG, Eble JA. Direct fibrinolytic snake venom metalloproteinases affecting hemostasis: Structural, biochemical features and therapeutic potential. Toxins (Basel) 2017; 9(12): 392.
[http://dx.doi.org/10.3390/toxins9120392] [PMID: 29206190]
[16]
Mihara H, Sumi H, Yoneta T, et al. A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus. Jpn J Physiol 1991; 41(3): 461-72.
[http://dx.doi.org/10.2170/jjphysiol.41.461] [PMID: 1960890]
[17]
Patel GK, Kawale AA, Sharma AK. Purification and physicochemical characterization of a serine protease with fibrinolytic activity from latex of a medicinal herb Euphorbia hirta. Plant Physiol Biochem 2012; 52: 104-11.
[http://dx.doi.org/10.1016/j.plaphy.2011.12.004] [PMID: 22305073]
[18]
Agrebi R, Haddar A, Hmidet N, Jellouli K, Manni L, Nasri M. BSF1 fibrinolytic enzyme from a marine bacterium Bacillus subtilis A26: Purification, biochemical and molecular characterization. Process Biochem 2009; 44(11): 1252-9.
[http://dx.doi.org/10.1016/j.procbio.2009.06.024]
[19]
Nascimento TP, Sales AE, Porto TS, et al. Purification, biochemical, and structural characterization of a novel fibrinolytic enzyme from Mucor subtilissimus UCP 1262. Bioprocess Biosyst Eng 2017; 40(8): 1209-19.
[http://dx.doi.org/10.1007/s00449-017-1781-3] [PMID: 28500420]
[20]
Matsubara K, Sumi H, Hori K, Miyazawa K. Purification and characterization of two fibrinolytic enzymes from a marine green alga, Codium intricatum. Comp Biochem Physiol B Biochem Mol Biol 1998; 119(1): 177-81.
[http://dx.doi.org/10.1016/S0305-0491(97)00303-9]
[21]
Chitte RR, Dey S. Potent fibrinolytic enzyme from a thermophilic Streptomyces megasporus strain SD5. Lett Appl Microbiol 2000; 31(6): 405-10.
[http://dx.doi.org/10.1046/j.1365-2672.2000.00831.x] [PMID: 11123546]
[22]
Peng Y, Yang X, Zhang Y. Microbial fibrinolytic enzymes: An overview of source, production, properties, and thrombolytic activity in vivo. Appl Microbiol Biotechnol 2005; 69(2): 126-32.
[http://dx.doi.org/10.1007/s00253-005-0159-7] [PMID: 16211381]
[23]
Chitte RR. Microbial source of fibrinolytic protease and its biotechnological potential. Springer: Heidelberg. 2013; pp. 79-88.
[http://dx.doi.org/10.1007/978-1-4614-9233-7_6]
[24]
Kotb E. Activity assessment of microbial fibrinolytic enzymes. Appl Microbiol Biotechnol 2013; 97(15): 6647-65.
[http://dx.doi.org/10.1007/s00253-013-5052-1] [PMID: 23812278]
[25]
Tillett WS, Garner RL. The fibrinolytic activity of hemolytic streptococci. J Exp Med 1933; 58(4): 485-502.
[http://dx.doi.org/10.1084/jem.58.4.485] [PMID: 19870210]
[26]
Gerheim EB. Staphylococcal coagulation and fibrinolysis. Nature 1948; 162(4123): 732.
[http://dx.doi.org/10.1038/162732a0] [PMID: 18892126]
[27]
Jeong YK, Park JU, Baek H, et al. Purification and biochemical characterization of a fibrinolytic enzyme from Bacillus subtilis BK-17. World J Microbiol Biotechnol 2001; 17: 89-92.
[http://dx.doi.org/10.1023/A:1016685411809]
[28]
Park SG, Kho CW, Cho S, Lee DH, Kim SH, Park BC. A functional proteomic analysis of secreted fibrinolytic enzymes from Bacillus subtilis 168 using a combined method of two-dimensional gel electrophoresis and zymography. Proteomics 2002; 2(2): 206-11.
[http://dx.doi.org/10.1002/1615-9861(200202)2:2<206::AID-PROT206>3.0.CO;2-5] [PMID: 11840566]
[29]
Jeong YK, Kim JH, Gal SW, et al. Molecular cloning and characterization of the gene encoding a fibrinolytic enzyme from Bacillus subtilis strain A1. World J Microbiol Biotechnol 2004; 20: 711-7.
[http://dx.doi.org/10.1007/s11274-003-4514-5]
[30]
Wang SH, Zhang C, Yang YL, Diao M, Bai MF. Screening of a high fibrinolytic enzyme producing strain and characterization of the fibrinolytic enzyme produced from Bacillus subtilis LD-8547. World J Microbiol Biotechnol 2007; 24: 475-82.
[http://dx.doi.org/10.1007/s11274-007-9496-2]
[31]
Wang S, Chen H, Liang T, et al. A novel nattokinase produced by Pseudomonas sp. TKU015 using Shrimp shells as substrate. Process Biochem 2009; 44: 70-6.
[http://dx.doi.org/10.1016/j.procbio.2008.09.009]
[32]
Wang SL, Wu YY, Liang TW. Purification and biochemical characterization of a nattokinase by conversion of shrimp shell with Bacillus subtilis TKU007. N Biotechnol 2011; 28(2): 196-202.
[http://dx.doi.org/10.1016/j.nbt.2010.09.003] [PMID: 20849993]
[33]
Wei X, Luo M, Xie Y, et al. Strain screening, fermentation, separation, and encapsulation for production of nattokinase functional food. Appl Biochem Biotechnol 2012; 168(7): 1753-64.
[http://dx.doi.org/10.1007/s12010-012-9894-2] [PMID: 22987066]
[34]
Egorov NS, Prianishnikova NI, Al’-Nuri MA, Aslanian RR. [Streptomyces spheroides M8-2 strain-a producer of extracellular proteolytic enzymes possessing fibrinolytic and thrombolytic action Nauchnye Doki Vyss Shkoly Biol Nauki 1985; 1(1): 77-81.
[PMID: 3882161]
[35]
Abdel-Naby MA, El-Diwany AI, Shaker HM, Ismail AM. Production and properties of fibrinolytic enzyme from Streptomyces sp.NRC 411. World J Microbiol Biotechnol 1992; 8(3): 267-9.
[http://dx.doi.org/10.1007/BF01201876] [PMID: 24425475]
[36]
Wang M, Wang J, Shao M, Wang M, Wang Y. [Fibrinolytic properties and thrombolytic effect of a novel fibrinolytic enzyme from Streptomyces sp. Y405 Yao Xue Xue Bao 1998; 33(7): 481-5.
[PMID: 12016879]
[37]
Gesheva V. Production of fibrinolytic enzyme by Streptomyces rimosus at conditions of nitrogen limitation. J Microb Biochem Technol 2009; 1: 57-8.
[http://dx.doi.org/10.4172/1948-5948.1000011]
[38]
Simkhada J, Mander P, Cho SS, Yoo JC. A novel fibrinolytic protease from Streptomyces sp. CS684. Process Biochem 2010; 45(1): 88-93.
[http://dx.doi.org/10.1016/j.procbio.2009.08.010]
[39]
Habib SA. Optimization of fibrinase productivity from Actinomycetes. Egypt J Hosp Med 2010; 40: 375-88.
[http://dx.doi.org/10.21608/ejhm.2010.17386]
[40]
Abdel-Fattah AF, Ismail AM. Purification and some properties of pure Cochliobolus lunatus fibrinolytic Enzyme. Biotechnol Bioeng 1984; 26(5): 407-11.
[http://dx.doi.org/10.1002/bit.260260502] [PMID: 18553333]
[41]
el-Aassar SA, el-Badry HM, Abdel-Fattah AF. The biosynthesis of proteases with fibrinolytic activity in immobilized cultures of Penicillium chrysogenum H9. Appl Microbiol Biotechnol 1990; 33(1): 26-30.
[http://dx.doi.org/10.1007/BF00170564] [PMID: 1367445]
[42]
El-Aassar SA. Production and properties enzyme in solid state cultures of Fusarium pallidoroseum. Biotechnol Lett 1995; 17: 943-8.
[http://dx.doi.org/10.1007/BF00127431]
[43]
Tao S, Peng L, Beihui L, Deming L, Zuohu L. Solid state fermentation of rice chaff for fibrinolytic enzyme production by Fusarium oxysporum. Biotechnol Lett 1997; 19: 465-7.
[http://dx.doi.org/10.1023/A:1018352328874]
[44]
Choi HS, Shin PH. Purification and partial characterization of a fibrinolytic protease in Pleurotus ostreatus. Mycology 1998; 90: 674-9.
[http://dx.doi.org/10.1080/00275514.1998.12026956]
[45]
Batomunkueva BP, Egorov NS. Isolation, purification and resolution of the extracellular proteinase complex of Aspergillus ochraceus 513 with fibrinolytic and anticoagulant activities. Microbiology 2001; 70(5): 519-22.
[http://dx.doi.org/10.1023/A:1012343718772] [PMID: 11763777]
[46]
Xiao-Lan L, Lian-Xiang D, Fu-Ping L, Xi-Qun Z, Jing X. Purification and characterization of a novel fibrinolytic enzyme from Rhizopus chinensis 12. Appl Microbiol Biotechnol 2005; 67(2): 209-14.
[http://dx.doi.org/10.1007/s00253-004-1846-5] [PMID: 15614557]
[47]
Haddar A, Agrebi R, Bougatef A, Hmidet N, Sellami-Kamoun A, Nasri M. Two detergent stable alkaline serine-proteases from Bacillus mojavensis A21: Purification, characterization and potential application as a laundry detergent additive. Bioresour Technol 2009; 100(13): 3366-73.
[http://dx.doi.org/10.1016/j.biortech.2009.01.061] [PMID: 19269812]
[48]
Kour D, Rana KL, Kaur T, et al. Extremophiles for hydrolytic enzymes productions: Biodiversity and potential biotechnological applications, bioprocessing for biomolecules production. Bioprocessing for Biomolecules Production. United States of America: John Wiley & Sons 2019; pp. 321-72.
[49]
Otohinoyi DA, Ibraheem O. Prospecting microbial extremophiles as valuable resources of biomolecules for biotechnological applications. Int J Sci Res (Ahmedabad) 2015; 4(1): 1042-59. [IJSR
[50]
Industrial Enzymes Market Size. 2020; Available at: . https://www.grandviewresearch.com/industry-analysis/industrial-enzymes-market
[51]
Ahuja K, Rawat A. Enzymes Market size by product. 2019; Available at: www.gminsights.com/industry-analysis/enzymes-market
[52]
Gwak JH, Sohn SY. Identifying the trends in wound-healing patents for successful investment strategies. PLoS One 2017; 12(3): e0174203.
[http://dx.doi.org/10.1371/journal.pone.0174203] [PMID: 28306732]
[53]
Kumar R, Tripathi RC, Singh V. Keyword based search and its limitations in the patent document to secure the idea from its infringement. Procedia Comput Sci 2016; 78: 439-46.
[http://dx.doi.org/10.1016/j.procs.2016.02.086]
[54]
Raddadi N, Cherif A, Daffonchio D, Neifar M, Fava F. Biotechnological applications of extremophiles, extremozymes and extremolytes. Appl Microbiol Biotechnol 2015; 99(19): 7907-13.
[http://dx.doi.org/10.1007/s00253-015-6874-9] [PMID: 26272092]
[55]
Dutta S, Lanvin B, Wunsch-Vincent S. Global Innovation Index. World Industrial Property Organization . 2019; Available at: https://www.wipo.int/edocs/pubdocs/pt/wipo_pub_gii_2019.pdf
[56]
Hertzfeld HR, Link A, Vonortas N. Intellectual property protection mechanisms in research partnerships. Res Policy 2006; 35(6): 825-38.
[http://dx.doi.org/10.1016/j.respol.2006.04.006]
[57]
Chitte RR, Dey S. Streptomyces megasporus sd5, process for the isolation thereof, novel fibrinolytic enzyme prepared therefrom, process for the production of said enzyme and method of treatment of thrombolytic disorders using said enzyme. US patent US20030170221, 2003.
[58]
Chitte RR, Dey S. Streptomyces megasporus sd5, process for the isolation thereof, novel fibrinolytic enzyme prepared therefrom, process for the production of said enzyme and method of treatment of thrombolytic disorders using said enzyme. US patent US6638503B2, 2003.
[59]
Rhee H, KIM HW. Bacillus subtilis strain for high yield of thrombolytic enzymes. JP2018525988A 2018.
[60]
Rhee H, Kim HW. Bacillus subtilis strain for high yield of thrombolytic enzymes. WO2017222141 2017.
[61]
Fall CJ, Törcsvári A, Benzineb K, Karetka G. Automated categorization in the international patent classification. SIGIR Forum. 37(1): 10-25.
[http://dx.doi.org/10.1145/945546.945547]
[62]
Montecchi T, Russo D, Liu Y. Searching in cooperative patent classification: Comparison between keyword and concept-based search. Adv Eng Inform 2013; 27(3): 335-45.
[http://dx.doi.org/10.1016/j.aei.2013.02.002]
[63]
IPC Inventory World Intellectual Property Organization (WIPO). 2020; Available at: https://www.wipo.int/classifications/ipc/ipcpub/
[64]
Sumi H, Hamada H, Tsushima H, Mihara H, Muraki H. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet. Experientia 1987; 43(10): 1110-1.
[http://dx.doi.org/10.1007/BF01956052] [PMID: 3478223]
[65]
Urano T, Ihara H, Umemura K, et al. The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis cleaves and inactivates plasminogen activator inhibitor type 1. J Biol Chem 2001; 276(6): 25690-4696.
[66]
Tai MW, Sweet BV. Nattokinase for prevention of thrombosis. Am J Health Syst Pharm 2006; 63(12): 1121-3.
[http://dx.doi.org/10.2146/ajhp050509] [PMID: 16754735]
[67]
Sumi H, Hamada H, Nakanishi K, Hiratani H. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990; 84(3): 139-43.
[http://dx.doi.org/10.1159/000205051] [PMID: 2123064]
[68]
Dabbagh F, Negahdaripour M, Berenjian A, et al. Nattokinase: Roduction and application. Appl Microbiol Biotechnol 98(22): 9199-206.
[http://dx.doi.org/10.1007/s00253-014-6135-3]
[69]
Kim JY, Gum SN, Paik JK, et al. Effects of nattokinase on blood pressure: A randomized, controlled trial. Hypertens Res 2008; 31(8): 1583-8.
[http://dx.doi.org/10.1291/hypres.31.1583] [PMID: 18971533]
[70]
Homma K, Wakana N, Suzuki Y, et al. Treatment of natto, a fermented soybean preparation, to prevent excessive plasma vitamin K concentrations in patients taking warfarin. J Nutr Sci Vitaminol (Tokyo) 2006; 52(5): 297-301.
[http://dx.doi.org/10.3177/jnsv.52.297] [PMID: 17190098]
[71]
Kim SB, Lee DW, Cheigh CI, et al. Purification and characterization of a fibrinolytic subtilisin-like protease of Bacillus subtilis TP-6 from an Indonesian fermented soybean, Tempeh. J Ind Microbiol Biotechnol 2006; 33(6): 436-44.
[http://dx.doi.org/10.1007/s10295-006-0085-4] [PMID: 16470353]
[72]
Cheigh CI, Cho SC, Choe EA, et al. Novel fibrinolytic protease. KR100753002B1, 2007.
[73]
Majumdar S, Dutta S, Das T, Chattopadhyay P, Mukherjee AK. Antiplatelet and antithrombotic activity of a fibrin(ogen)olytic protease from Bacillus cereus strain FF01. Int J Biol Macromol 2015; 79: 477-89.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.04.075] [PMID: 25964180]
[74]
Rahul K, Kirti V, Sharma RC. Thermophilic microbial diversity and physicochemical attributes of thermal springs in the Garhwal Himalaya. Environ Exp Biol 2020; 18(2): 143-52.
[75]
Dey S, Chitte RR. A new thrombolytic enzyme for acute myocardial infarction. Med Chem Res 2001; 10(7): 507-15.
[76]
Chitte RR, Deshmukh SV, Kanekar PP. Production, purification, and biochemical characterization of a fibrinolytic enzyme from thermophilic Streptomyces sp. MCMB-379. Appl Biochem Biotechnol 2011; 165(5-6): 1406-13.
[http://dx.doi.org/10.1007/s12010-011-9356-2] [PMID: 21909629]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy