An Overview of Papain Enzyme Characteristics, Applications and Production

Document Type : Original Article

Authors

1 Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

2 Department of Biology, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran

Abstract

Enzymatic processing, a longstanding practice in biotechnology, leverages enzymes as eco-friendly catalysts for biochemical reactions. Papain is one of the most significant cysteine proteases derived from the latex of the unripe papaya plant. Papain has gained significant attention for its diverse applications in the food, pharmaceutical, and cosmetics industries. The industrial-scale production of papain is essential to satisfy the growing global demand for this enzyme. This paper highlights the versatility and economic relevance of papain, providing insights into its characteristics, production methods, and expanding market trends in various industries while highlighting the synergy between natural resources and biotechnological advancement. For this purpose, we performed a comprehensive literature analysis of the papain enzyme, spanning from January 1961 to May 2024, with Google Scholar as our main source of information.

Keywords

References

Abdeldaiem AM, El-Bagoury EH, Abbas F, Faisal MA. (2019). Effect of some factors on the proteolytic activities of bromelain, Cichorium, and Papain extracts. Ismailia Journal of Dairy Science & Technology. 6 (1): 1-7. https://ijds.journals.ekb.eg/article_69351.html.
Ahmed S, Birlie A, Admasu K. (2024). Investigating the Papain Enzyme’s Potential for Sheepskin Unhairing. DOI: https://doi.org/10.21203/rs.3.rs-4099090/v1.
Amri E and Mamboya F. (2012). Papain, a plant enzyme of biological importance: A review. In American Journal of Biochemistry and Biotechnology. 8 (2): 99--104. DOI: https://doi.org/10.3844/ajbbsp.2012.99.104.
Anfinsen CB and Haber E. (1961). Studies on the Reduction and Re-formation of Protein Disulfide Bonds. In The Journal of Biological Chemistry. 236 (5): 1361-1363. DOI: https://doi.org/10.1016/S0021-9258(18)64177-8.
Ayodipupo Babalola B, Ifeolu Akinwande A, Otunba A A, Ebenezer Adebami G, Babalola O, Nwuofo C. (2024). Therapeutic benefits of Carica papaya: A review on its pharmacological activities and characterization of papain. Arabian Journal of Chemistry. 17 (1). DOI: https://doi.org/10.1016/j.arabjc.2023.105369.
Baines B S, and Brocklehurstt K. (1979). A Necessary Modification to the Preparation of Papain from Any High-Quality Latex of Carica papaya and Evidence for the Structural Integrity of the Enzyme Produced by Traditional Methods. The Biochemical Journal. Biochem J (1979) 177 (2): 541-548. DOI: https://doi.org/10.1042/bj1770541.
Banchhor M and Saraf S. (2008). Phcog Rev.: Potentiality of Papain as an Antiaging Agent in cosmetic formulation. Pharmacognosy Reviews. 2 (4): 266-270. https://phcogrev.com/sites/default/files/PhcogRev-2-4-266.pdf.
Barekat S and Soltanizadeh N. (2017). Improvement of meat tenderness by simultaneous application of high-intensity ultrasonic radiation and papain treatment. Innovative Food Science and Emerging Technologies. 39: 223-229. DOI: https://doi.org/10.1016/j.ifset.2016.12.009.
Beilen JB van and Li Z. (2002). Enzyme technology: An overview. Current opinion in biotechnology. 13 (4): 338-344. DOI: https://doi.org/10.1016/S0958-1669(02)00334-8.
Benavides J, Aguilar O, Lapizco-Encinas BH, Rito-Palomares M. (2008). Extraction and purification of bioproducts and nanoparticles using aqueous two-phase systems strategies. In Chemical Engineering and Technology. 31 (6): 838-845. DOI: https://doi.org/10.1002/ceat.200800068.
Brömme D, Nallaseth FS, Turk B. (2004). Production and activation of recombinant papain-like cysteine proteases. Methods. 32 (2): 199-206. DOI: https://doi.org/10.1016/S1046-2023(03)00212-3.
Channamade C, Raju JM, Vijayaprakash SB, Bora R, Shekhar NR. (2021). Promise approach on chemical stability enhancement of papain by encapsulation system: a review. Journal of Young Pharmacists, 13(2), 87-90. DOI: https://doi.org/10.5530/jyp.2021.13.20.
Choi JM, Han SS, Kim HS. (2015). Industrial applications of enzyme biocatalysis: Current status and future aspects. Biotechnology Advances. 33 (7): 1443-1454. DOI: https://doi.org/10.1016/j.biotechadv.2015.02.014.
Choudhury D, Roy S, Chakrabarti C, Biswas S, and Dattagupta J K. (2009). Production and recovery of recombinant propapain with high yield. Phytochemistry. 70 (4): 465-472. DOI: https://doi.org/10.1016/j.phytochem.2009.02.001.
Choudhury P, and Bhunia B. (2015). Industrial application of lipase: a review. Biopharm Journal. 2: 41-47. www.biopharmj.com.
Cohen LW, Coghlan VM, Dihel LC. (1986). Cloning and sequencing of papain-encoding cDNA (Carica papaya; zymogen; amino acid change; recombinant DNA). Gene. 48 (2-3): 219-227. DOI: https://doi.org/10.1016/0378-1119(86)90080-6.
Debata NB, Sahoo HS, Paital B. (2021). Artificial superoxide dismutase for cosmetic therapy and industrial use Related papers. Academia Letters, April 2021. DOI: https://doi.org/10.20935/AL913.
Dennison C and Lovrien R. (1997). Three phase partitioning: concentration and purification of proteins. protein expression and purification. 11 (2): 149-161. DOI: https://doi.org/10.1006/prep.1997.0779.
Dhivya R, Sherin Rashma R, Vinothini B, Pavithra R. (2018). Extraction and purification of papain enzyme from Carica papaya for wound debridement. International Journal of Pure and Applied Mathematics. 119 (15): 1265-1274.
dos Anjos MM, da Silva AA, de Pascoli IC, Mikcha JMG, Machinski M, Peralta RM, de Abreu Filho BA. (2016). Antibacterial activity of papain and bromelain on Alicyclobacillus spp. International Journal of Food Microbiology. 216: 121-126. DOI: https://doi.org/10.1016/j.ijfoodmicro.2015.10.007.
dos Santos Bazanella GC, de Souza DF, Castoldi R, Oliveira RF, Bracht A, Peralta RM. (2013). Production of laccase and manganese peroxidase by Pleurotus pulmonarius in solid-state cultures and application in dye decolorization. Folia Microbiologica, 58 (6): 641-647. DOI: https://doi.org/10.1007/s12223-013-0253-7.
Dubois O, Thierry Kleinschmidt T, Schnek, A G, LoozeY, and Braunitzer G. (1988). The thiol proteinases from the latex of carica papaya L. II. the primary structure of proteinase Ω". Biological Chemistry. 369 (2): 741-745. https://doi.org/10.1515/bchm3.1988.369.2.741.
Eshamah H, Han I, Naas H, Acton J, Dawson P. (2014). Antibacterial effects of natural tenderizing enzymes on different strains of Escherichia coli O157:H7 and Listeria monocytogenes on beef. Meat Science, 96(4), 1494-1500. DOI: https://doi.org/10.1016/j.meatsci.2013.12.010.
Fazolin G N, Varca G H C, Kadlubowski S, Sowinski S, Lugão AB. (2020). The effects of radiation and experimental conditions over papain nanoparticle formation: Towards a new generation synthesis. Radiation Physics and Chemistry. 169: 107984. DOI: https://doi.org/10.1016/j.radphyschem.2018.08.033.
Garcia S, and Gonçalves D, Gonçalves S. (2021). Use of enzymes in cosmetics: proposed enzymatic peel procedure. Cos Active Journal. 1:29-35
Gaur N, Narasimhulu K, Pydisetty Y. (2018). Biochemical and kinetic characterization of laccase and manganese peroxidase from novel: Klebsiella pneumoniae strains and their application in bioethanol production. RSC Advances. 8 (27): 15044-15055. DOI: https://doi.org/10.1039/c8ra01204k.
Gorokhovets NV, Makarov VA, Petushkova AI, Prokopets OS, Rubtsov MA, Savvateeva LV, Zernii EY, Zamyatnin AA. (2017). Rational design of recombinant papain-like cysteine protease: Optimal domain structure and expression conditions for wheat-derived enzyme Triticain-α. International Journal of Molecular Sciences. 18 (7): DOI: https://doi.org/10.3390/ijms18071395. Corpus ID: 4237540.
Hastuti N, Agustini L, Hardiningtyas SD, Ramadhan W, Indrawan DA, Ismayati M, Tazkiatunnisa A. (2024). Microfibrillated cellulose made of agar waste in alginate-based hydrogels for papain enzyme immobilization. AIP Conference Proceedings. 2973 (1). DOI: https://doi.org/10.1063/5.0184557.
Jain J and Student MS. (2020). Review on isolation and purification of papain enzyme from papaya fruit. International Journal of Engineering Applied Sciences and Technology. 5: 193-197. DOI: https://doi.org/10.33564/IJEAST.2020.v05i06.028.
Jakfar Husin H, Pontas K, Mamat R, Salleh MR, Zulrika M, Ahmadi A. (2023). Modification of the fermentation process and papain enzymes in the manufacture of virgin coconut oil using optimization of response surface methodology, central composite design. Fermentation. 9 (5): 434. DOI: https://doi.org/10.3390/fermentation9050434.
Jame-Chenarboo F, Aliahmadi A, Khavari S, Habibi F, Esmaeili R, and Ghassempour A. (2022). Functional analysis of recombinant menthone menthol reductase by chiral GC and GC-MS. Industrial Crops and Products. 184: 115075. DOI: https://doi.org/10.1016/j.indcrop.2022.115075.
Janetzki JL, Pratt NL, Ward MB, Sykes MJ. (2023). Application of an integrative drug safety model for detection of adverse drug events associated with inhibition of glutathione peroxidase 1 in chronic obstructive pulmonary disease. Pharmaceutical Research. 40 (6): 1553-1568. DOI: https://doi.org/10.1007/s11095-023-03516-x.
Jegannathan KR, and Nielsen PH. (2013). Environmental assessment of enzyme uses in industrial production-a literature review. Journal of Cleaner Production. 42: 228-240. DOI: https://doi.org/10.1016/j.jclepro.2012.11.005.
Jeon G, Kim C, Cho UM, Hwang ET, Hwang HS, Min J. (2021). Melanin-decolorizing activity of antioxidant enzymes, glutathione peroxidase, thiol peroxidase, and catalase. Molecular Biotechnology. 63 (2): 150-155. DOI: https://doi.org/10.1007/s12033-020-00292-6.
Joshi DN. (2015). Extraction and application of papain enzyme on degradation of drug. International Journal of Pharmacy and Biological Sciences. 1 (1). https://ijsrst.com/home/issue/view/article.php?id=IJSRST173894.
Jung E, Lee J, Baek J, Jung K, Lee J, Huh S, Kim S, Koh J, and Park D. (2007). Effect of Camellia japonica oil on human type I procollagen production and skin barrier function. Journal of Ethnopharmacology. 112 (1): 127-131. DOI: https://doi.org/10.1016/j.jep.2007.02.012.
 
Jurkevicz CS, de Araujo Porto FV, Tischer CA, Fronza M, Endringer DC, Ribeiro-Viana RM. (2024). Papain covalent immobilization in bacterial cellulose films as a wound dressing. Journal of Pharmaceutical Sciences. 113 (2): 427-433. DOI: https://doi.org/https://doi.org/10.1016/j.xphs.2023.11.015.
Kant Bhatia S, Vivek N, Kumar V, Chandel N, Thakur M, Kumar D, Yang YH, Pugazendhi A, Kumar G. (2021). Molecular biology interventions for activity improvement and production of industrial enzymes. Bioresource Technology. 324: 124596. Elsevier Ltd. DOI: https://doi.org/10.1016/j.biortech.2020.124596.
Krishnamoorthy G, Saxena A, Mars LT, Domingues HS, Mentele R, Ben-Nun A, Lassmann H, Dornmair K, Kurschus F C, Liblau R S, Wekerle H. (2009). Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis. Nature Medicine. 15 (6): 626-632. DOI: https://doi.org/10.1038/nm.1975.
Lapuente Salinas E. (2021). Papain extraction from papaya and determination of the enzyme activity. DOI: http://hdl.handle.net/2445/185820.
Lee K L, and Chong C C. (2011). The use of reverse micelles in downstream processing of biotechnological products. DOI: https://doi.org/10.48550/arXiv.1109.1641.
Lehmann P V, Forsthuber T, Miller A, Sercarz E E. (1992). Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature. 9: 358(6382): 155-7. DOI: https://doi.org/10.1038/358155a0.
Lester G E, Hodges D M, Meyer R D, Munro K D. (2004). Pre-extraction preparation (fresh, frozen, freeze-dried, or acetone powdered) and long-term storage of fruit and vegetable tissues: effects on antioxidant enzyme activity. Journal of Agricultural and Food Chemistry. 52 (8): 2167-2173. DOI: https://doi.org/10.1021/jf030713b.
Light A, Frater R, Kimmel JR, Smith E L. (1964). Current status of the structure of papain: the linear sequence, active sulfhydryl group, and the disulfide bridges. 52 (5): 1276-1283. DOI: https://doi.org/10.1073/pnas.52.5.1276.
Ling C, Zhang J, Lin D, Tao A. (2015). Approaches for the generation of active papain-like cysteine proteases from inclusion bodies of Escherichia coli. World Journal of Microbiology and Biotechnology. 31 (5): 681-690. Kluwer Academic Publishers. DOI: https://doi.org/10.1007/s11274-015-1804-7.
Mohamed SH, Mohamed MSM, Khalil MS, Mohamed WS, Mabrouk MI. (2018). Antibiofilm activity of papain enzyme against pathogenic Klebsiella pneumoniae. Journal of Applied Pharmaceutical Science. 8 (6): 163-168. DOI: https://doi.org/10.7324/JAPS.2018.8621.
Moreira Filho RNF, Vasconcelos NF, Andrade FK, Rosa MdeF, Vieira RS. (2020). Papain immobilized on alginate membrane for wound dressing application. Colloids and Surfaces B: Biointerfaces. 194. DOI: https://doi.org/10.1016/j.enzmictec.2006.02.013.
Nekouei M., Ghezellou P., Aliahmadi A, Arjmand S, Kiaei M, Ghassempour A. (2018). Changes in biophysical characteristics of PFN1 due to mutation causing amyotrophic lateral sclerosis. Metabolic Brain Disease. 33: 1975–1984. DOI: https://doi.org/10.1007/s11011-018-0305-4.
Nordin NDB. (2010). The extraction of papain from papaya leaves. DOI: http://umpir.ump.edu.my/3428/1/CD5957_Nur_Dianaty_Nordin.pdf.
Oliver-Simancas R, Labrador-Fernández L, Abellán-Diéguez C, García-Villegas A, Del Caro A, Leyva-Jimenez FJ, Alañón ME. (2024). Valorization applications of pineapple and papaya byproducts in the food industry. In Comprehensive Reviews in Food Science and Food Safety. 23: (3). DOI: https://doi.org/10.1111/1541-4337.13359.
Ozhelvaci F and Steczkiewicz K. (2023). Identification and classification of papain-like cysteine proteinases. Journal of Biological Chemistry. 299 (6). DOI: https://doi.org/10.1016/j.jbc.2023.104801.
Paul B, Nasreen M, Sarker A, Islam M R. (2013). Isolation, purification, and modification of enzyme to ascertain industrially valuable nature. International Journal of Bio-Technology and Research. 3 (5): 11-22.
Miles C L, Lawrie R A. (1970). Relation between pH and tenderness in cooked muscle. International Journal of Food Science and Technology. 5 (4): 325-330. https://doi.org/10.1111/j.1365-2621.1970.tb01576.x.
Rinaldi F, Tengattini S, Brusotti G, Tripodo G, Peters B, Temporini C, Massolini G, Calleri E. (2021). Monolithic papain-immobilized enzyme reactors for automated structural characterization of monoclonal antibodies. Frontiers in Molecular Biosciences. 8. DOI: https://doi.org/10.3389/fmolb.2021.765683.
Sharafeddin F, Jowkar Z, Safari M. (2024). Effects of different concentrations of bromelain and papain enzymes on shear bond strength of composite resin to deep dentin using an etch-and-rinse adhesive system. Dental and Medical Problems. 61 (1): 85-91. DOI: https://doi.org/10.17219/dmp/133404.
Shin SK, Hyeon JE, Joo YC, Jeong DW, You SK, Han SO. (2019). Effective melanin degradation by a synergistic laccase-peroxidase enzyme complex for skin whitening and other practical applications. International Journal of Biological Macromolecules. 129: 181-186. DOI: https://doi.org/10.1016/j.ijbiomac.2019.02.027.
Shouket H A, Ameen I, Tursunov O, Kholikova K, Pirimov O, Kurbonov N, Ibragimov I, and Mukimov, B. (2020). Study on industrial applications of papain: A succinct review. IOP Conference Series: Earth and Environmental Science. 614: 012171. DOI: https://doi.org/10.1088/1755-1315/614/1/012171.
Sim YC, Lee SG, Lee DC, Kang BY, Park KM, Lee JY, Kim MS, Chang IS, Rhee JS. (2000). Stabilization of papain and lysozyme for application to cosmetic products. Biotechnology Letters. 22: 137–140. DOI: http://dx.doi.org/10.1023/A:1005670323912.
Syahdan, Moch GM, Andiana P, Radiati LE. (2024). Emulsifying and lipid peroxidation inhibitory activities of chicken head protein hydrolysate using a combination of papain and Bromelain Enzymes. Asian Food Science Journal. 23 (2): 17-25. DOI: https://doi.org/10.9734/afsj/2024/v23i2698.
Tacias-Pascacio VG, Castañeda-Valbuena D, Morellon-Sterling R, Tavano O, Berenguer-Murcia Á, Vela-Gutiérrez G, Rather IA, Fernandez-Lafuente R. (2021). Bioactive peptides from fisheries residues: A review of use of papain in proteolysis reactions. International Journal of Biological Macromolecules. 184: 415-428. DOI: https://doi.org/10.1016/j.ijbiomac.2021.06.076.
Taylor M AJ, Pratt KA, Reveu DF, Baker KC, Sumner IG, Goodenough PW. (1992). Active papain renatured and processed from insoluble recombinant propapain expressed in Escherichia coli. Protein Engineering. 5 (5): 455-459. DOI: https://doi.org/10.1093/protein/5.5.455.
Tigist M, Getnet B, Beza K, Endalamaw M, Lulit M, Tamirat D, Tinsae M. (2016). Extraction and purification of papain enzyme from papaya leaf and the phytochemical components of the leaf. Biotechnology International. 9(8), 176-184.
Tsuge H, Nishimura T, Tada Y, Asao T, Turk D, Turk V, Katunuma N. (1999). Inhibition mechanism of cathepsin L-specific inhibitors based on the crystal structure of papain-CLIK148 complex. Biochemical and Biophysical Research Communications. 266 (2): 411-416. DOI: https://doi.org/10.1006/bbrc.1999.1830.
Werner N, Hirth T, Rupp S, Zibek S. (2015). Expression of a codon-optimized Carica papaya papain sequence in the methylotrophic yeast Pichia pastoris. Journal of Microbial and Biochemical Technology. 7 (5). DOI: https://doi.org/10.4172/1948-5948.1000231.
Yulirohyami, Istiningrum RB, Puspasari I, Wijaya AR, Hidayat H. (2024). Papain assisted preparation of chitosan: Feasibility study for candidate in-house reference material and antibacterial agent. Food and Humanity. 2: 100313. DOI: https://doi.org/10.1016/j.foohum.2024.100313.
Plant, Algae, and Environment
Volume 8, Issue 2
2024
Pages 1505-1527

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