Skip to main content

Advertisement

Log in

Native and Biotechnologically Engineered Plant Proteases with Industrial Applications

  • Original Paper
  • Published:
Food and Bioprocess Technology Aims and scope Submit manuscript

Abstract

Proteases occupy the most relevant position among industrial enzymes. Plant proteases have been used in medicine, detergent manufacturing, and food science for many years, but their production is diminishing in favor of those of microbial origin because lower production costs. Papain, bromelain, and ficin are the most frequently employed plant proteases, although new proteases with new and more appealing physicochemical properties for industry are still emerging. DNA technology and genetic engineering shall play, without a doubt, an important role for the production of these proteases at the industrial level. The present review focuses on the applications of traditional plant proteases as well as new proteases discovered during the last 20 years, some of which have already been genetically engineered either to increase production or to strengthen some of their physicochemical properties. The review also refers to the protease classification, action pattern, and main characteristics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aehle, W. (2004). Industrial enzymes: Enzymes in food applications. In W. Aehle (Ed.), Enzymes in industry: Production and applications. Chichester: Wiley.

    Google Scholar 

  • Antao, C. M., & Malcata, F. X. (2005). Plant serine proteases: biochemical, physiological and molecular features. Plant Physiology and Biochemistry, 43(7), 637–650.

    CAS  Google Scholar 

  • Arima, K., Uchikoba, T., Yonezawa, H., Shimada, M., & Kaneda, M. (2000). Cucumisin-like protease from the latex of Euphorbia supina. Phytochemistry, 53(6), 639–644.

    CAS  Google Scholar 

  • Asakura, T., Watanabe, H., Abe, K., & Arai, S. (1995). Rice aspartic proteinase, oryzasin, expressed during seed ripening and germination has a gene organization distinct from those of animal and microbial aspartic proteinases. European Journal of Biochemistry, 232(1), 77–83.

    CAS  Google Scholar 

  • Asakura, T., Watanabe, H., Abe, K., & Arai, S. (1997). Oryzasin as an aspartic proteinase occurring in rice seeds: purification, characterization, and application to milk clotting. Journal of Agricultural and Food Chemistry, 45(4), 1070–1075.

    CAS  Google Scholar 

  • Asif-Ullah, M., Kim, K. S., & Yu, Y. G. (2006). Purification and characterization of a serine protease from Cucumis trigonus Roxburghi. Phytochemistry, 67(9), 870–875.

    CAS  Google Scholar 

  • Aspmo, S. I., Horn, S. J., & Eijsink, V. G. H. (2005). Enzymatic hydrolysis of Atlantic cod (Gadus morhua L.) viscera. Process Biochemistry, 40(5), 1957–1966.

    CAS  Google Scholar 

  • Azarkan, M., El Moussaoui, A., Van Wuytswinkel, D., Dehon, G., & Looze, Y. (2003). Fractionation and purification of the enzymes stored in the latex of Carica papaya. Journal of Chromatography. B: Analytical Technologies in the Biomedical and Life Sciences, 790(1–2), 229–238.

    CAS  Google Scholar 

  • Baines, B. S., & Brocklehurst, K. (1979). A necessery modification to the preparation of papain from any high-quality latex of Carica papaya and evidence for structural integrity of the enzyme produced by traditional methods. The Biochemical Journal, 177(2), 541–548.

    CAS  Google Scholar 

  • Barbas, C. F., & Wong, C. H. (1987). Papain catalysed peptide synthesis: Control of amidase activity and the introduction of unusual amino acids. Journal of the Chemical Society, 1987, 533–534.

    Google Scholar 

  • Barrett, A. J. (1994). Classification of Peptidases. Methods in Enzymology, 244, 1–15.

    CAS  Google Scholar 

  • Beers, E. P., Jones, A. M., & Dickerman, A. W. (2004). The S8 serine, C1A cysteine and A1 aspartic protease families in Arabidopsis. Phytochemistry, 65(1), 43–58.

    CAS  Google Scholar 

  • Behnke, J. M., Buttle, D. J., Stepek, G., Lowe, A., & Duce, I. R. (2008). Developing novel anthelmintics from plant cysteine proteinases. Parasites & Vectors, 1(1), 29.

    Google Scholar 

  • Belozersky, M. A., Sarbakanova, S. T., & Dunaevsky, Y. E. (1989). Aspartic proteinase from wheat seeds—isolation, properties and action on gliadin. Planta, 177(3), 321–326.

    Google Scholar 

  • Berger, D., & Altmann, T. (2000). A subtilisin-like serine protease involved in the regulation of stomatal density and distribution in Arabidopsis thaliana. Genes & Development, 14(9), 1119–1131.

    CAS  Google Scholar 

  • Berger, J., & Asenjo, C. F. (1940). Anthelmintic activity of crystalline papain. Science, 91(2364), 387–388.

    CAS  Google Scholar 

  • Beuth, J. (2008). Proteolytic enzyme therapy in evidence-based complementary oncology: fact or fiction? Integrative Cancer Therapies, 7(4), 311–316.

    CAS  Google Scholar 

  • Boguslawski, S. J., Ledden, D. J., & Fredrickson, R. A. (1989). Improved procedure for preparation of F(ab’)2 fragments of mouse IgGs by papain digestion. Journal of Immunological Methods, 120(1), 51–56.

    CAS  Google Scholar 

  • Brien, S., Lewith, G., Walker, A., Hicks, S. M., & Middleton, D. (2004). Bromelain as a treatment for osteoarthritis: a review of clinical studies. Evidence-Based Complementary Alternative Medicine, 1(3), 251–257.

    Google Scholar 

  • Burton, S. G., Cowan, D. A., & Moodley, J. M. (2002). The search for the ideal biocatalyst. Nature Biotechnology, 20(1), 37–45.

    CAS  Google Scholar 

  • Buttle, D. J., Kembhavi, A. A., Sharp, S. L., Shute, R. E., Rich, D. H., & Barrett, A. J. (1989). Affinity purification of the novel cysteine proteinase papaya proteinase IV, and papain from papaya latex. The Biochemical Journal, 261(2), 469–476.

    CAS  Google Scholar 

  • Cáceres Arriba, P. & Fernández, J.I. (2000) Proceso de obtención de extractos en polvo de un coagulante de leche procedente de las flores del cardo Cynara sp. Patente Espanhola ES 2 139 550 A1

  • Campos, R., Guerra, R., Aguilar, M., Ventura, O., & Camacho, L. (1990). Chemical characterization of proteases extracted from wild thistle (Cynara cardunculus). Food Chemistry, 35(2), 89–97.

    CAS  Google Scholar 

  • Carter, C. E., Marriage, H., & Goodenough, P. W. (2000). Mutagenesis and kinetic studies of a plant cysteine proteinase with an unusual arrangement of acidic amino acids in and around the active site. Biochemistry, 39(36), 11005–11013.

    CAS  Google Scholar 

  • Castanheira, P., Samyn, B., Sergeant, K., Clemente, J. C., Dunn, B. M., Pires, E., et al. (2005). Activation, proteolytic processing, and peptide specificity of recombinant cardosin A. The Journal of Biological Chemistry, 280(13), 13047–13054.

    CAS  Google Scholar 

  • CFR(Code of Federal Regulations). (1999). Bacterially-derived protease enzyme preparation (No.21, Section 1150). Washington,DC: CFR.

    Google Scholar 

  • CFR(Code of Federal Regulations). (2009). Use of food ingredients and sources of ratiation (No.21, Section 21). Washington,DC: CFR.

    Google Scholar 

  • Chen, F., & Foolad, M. R. (1997). Molecular organization of a gene in barley which encodes a protein similar to aspartic protease and its specific expression in nucellar cells during degeneration. Plant Molecular Biology, 35(6), 821–831.

    CAS  Google Scholar 

  • Chen, Y.-X., Zhang, X.-Z., Zheng, K., Chen, S.-M., Wang, Q.-C., & Wu, X.-X. (1998). Protease-catalyzed synthesis of precursor dipeptides of RGD with reverse micelles. Enzyme and Microbial Technology, 23(3–4), 243–248.

    CAS  Google Scholar 

  • Cherry, J. R., & Fidantsef, A. L. (2003). Directed evolution of industrial enzymes: an update. Current Opinion in Biotechnology, 14(4), 438–443.

    CAS  Google Scholar 

  • Chitpinitoyl, S., & Crabbe, M. J. C. (1998). Chymosin and aspartic proteinases. Food Chemistry, 61, 395–418.

    Google Scholar 

  • Choudhury, D., Biswas, S., Roy, S., & Dattagupta, J. K. (2010). Improving thermostability of papain through structure-based protein engineering. Protein Engineering, Design & Selection, 23(6), 457–467.

    CAS  Google Scholar 

  • Choudhury, D., Roy, S., Chakrabarti, C., Biswas, S. & Dattagupta, J,K, (2009). Production and recovery of recombinant propapain with high yield, 70(4), 465–72.

  • Coffeen, W. C., & Wolpert, T. J. (2004). Purification and characterization of serine proteases that exhibit caspase-like activity and are associated with programmed cell death in Avena sativa. The Plant Cell, 16(4), 857–873.

    CAS  Google Scholar 

  • Cohen, L. W., Coghlan, V. M., & Dihel, L. C. (1986). Cloning and sequencing of papain-encoding cDNA. Gene, 48(2–3), 219–227.

    CAS  Google Scholar 

  • Cohen, L. W., Fluharty, C., & Dihel, L. C. (1990). Synthesis of papain in Escherichia coli. Gene, 88(2), 263–267.

    CAS  Google Scholar 

  • Cooreman, W. (1978). In R. Ruyssen & A. Lauwers (Eds.), VIII. Bromelain. In: Pharmaceutical enzymes properties and assay methods (pp. 107–121). Belgium: E. Story-Scientia Scientific Publishing Co. Gent.

    Google Scholar 

  • Cordeiro, M. C., Xue, Z. T., Pietrzak, M., Pais, M. S., & Brodelius, P. E. (1994). Isolation and characterization of a cDNA from flowers of Cynara cardunculus encoding cyprosin (an aspartic proteinase) and its use to study the organ-specific expression of cyprosin. Plant Molecular Biology, 24(5), 733–741.

    CAS  Google Scholar 

  • D’Hondt, K., Stack, S., Gutteridge, S., Vandekerckhove, J., Krebbers, E., & Gal, S. (1997). Aspartic proteinase genes in the Brassicaceae Arabidopsis thaliana and Brassica napus. Plant Molecular Biology, 33(1), 187–192.

    Google Scholar 

  • De Clerck, J. (1969). The use of proteolytic enzymes for the stabilization of beer. Technology Q Master Brew Association American, 6, 136–140.

    Google Scholar 

  • Devakate, R. V., Patil, V. V., Waje, S. S., & Thorat, B. N. (2009). Purification and drying of bromelain. Separation and Purification Technology, 64(3), 259–264.

    CAS  Google Scholar 

  • Devaraj, K. B., Kumar, P. R., & Prakash, V. (2008). Purification, characterization, and solvent-induced thermal stabilization of ficin from Ficus carica. Journal of Agricultural and Food Chemistry, 56(23), 11417–11423.

    CAS  Google Scholar 

  • Díaz, O., Fernandéz, M., Gracia de Fernando, C. D., de la Hoz, L., & Ordóñez, J. A. (1996). Effect of the addition of papain on the dry fermented sausage proteolysis. Journal of the Science of Food and Agriculture, 71(1), 13–21.

    Google Scholar 

  • Distefano, S., Palma, J. M., McCarthy, I., & Del Rio, L. A. (1999). Proteolytic cleavage of plant proteins by peroxisomal endoproteases from senescent pea leaves. Planta, 209(3), 308–313.

    CAS  Google Scholar 

  • Domingos, A., Cardoso, P. C., Xue, Z., Clemente, A., Brodelius, P. E., & Pais, M. S. (2000). Purification, cloning and autoproteolytic processing of an aspartic proteinase from Centaurea calcitrapa. European Journal of Biochemistry, 267(23), 6824–6831.

    CAS  Google Scholar 

  • Drenth, J., Jansonius, J. N., Koekoek, R., Swen, H. M., & Wolthers, B. G. (1968). Structure of papain. Nature, 218, 929–932.

    CAS  Google Scholar 

  • Driska, S. P., Laudadio, R. E., Wolfson, M. R., & Shaffer, T. H. (1999). A method for isolating adult and neonatal airway smooth muscle cells and measuring shortening velocity. Journal of Applied Physiology, 86(1), 427–435.

    CAS  Google Scholar 

  • Dubey, V. K., Pande, M., Singh, B. K., & Jagannadham, M. V. (2007). Papain-like proteases: applications of their inhibitors. African Journal of Biotechnology, 6(9), 1077–1086.

    CAS  Google Scholar 

  • Dubois, T., Kleinschmidt, T., Schnek, A. G., Looze, Y., & Braunitzer, G. (1988). The thiol proteinases from the latex of Carica papaya L. II. The primary structure of proteinase omega. Biological Chemistry Hoppe-Seyler, 369(8), 741–754.

    CAS  Google Scholar 

  • Dufour, E., Storer, A. C., & Ménard, R. (1995). Engineering nitrile hydratase activity into a cysteine protease by a single mutation. Biochemistry, 34(50), 16382–16388.

    CAS  Google Scholar 

  • Dufour, E., Tam, W., Nägler, D. K., Storer, A. C., & Ménard, R. (1998). Synthesis of amidrazones using an engineered papain nitrile hydratase. FEBS Letters, 433(1–2), 78–82.

    CAS  Google Scholar 

  • Dunn, B. M. (2001). (2001) Determination of protease mechanism. In R. Beynon & J. S. Bond (Eds.), Plant proteolytic enzymes—a practical approach (pp. 77–79). New York: Oxford University Press.

    Google Scholar 

  • Egas, C., Lavoura, N., Resende, R., Brito, R. M. M., Pires, E., Pedroso de Lima, M. C., et al. (2000). The saposin-like domain of the plant aspartic proteinase precursor is a potent inducer of vesicle leakage. The Journal of Biological Chemistry, 275(49), 38190–38196.

    CAS  Google Scholar 

  • Faro, C., Ramalho-Santos, M., Vieira, M., Mendes, A., Simões, I., Andrade, R., et al. (1999). Cloning and characterization of cDNA encoding cardosin A, an RGD-containing plant aspartic proteinase. The Journal of Biological Chemistry, 274(40), 28724–28729.

    CAS  Google Scholar 

  • Faro, C., Verissimo, P., Lin, Y., Tang, J., & Pires, E. (1995). Cardosin A and B, aspartic proteases from the flowers of cardoon. Advances in Experimental Medicine and Biology, 362, 373–377.

    CAS  Google Scholar 

  • Fernández-Salguero, J., Prados, F., Calixto, F., Vioque, M., Sampaio, P., & Tejada, L. (2003). Use of recombinant cyprosin in the manufacture of ewe’s milk cheese. Journal of Agricultural and Food Chemistry, 51(25), 7426–7430.

    Google Scholar 

  • Fonseca, K. C., Morais, N. C., Queiroz, M. R., Silva, M. C., Gomes, M. S., Costa, J. O., et al. (2010). Purification and biochemical characterization of Eumiliin from Euphorbia milii var. hislopii latex. Phytochemistry, 71(7), 708–715.

    CAS  Google Scholar 

  • Frazão, C., Bento, I., Costa, J., Soares, C. M., Veríssimo, P., Faro, C., et al. (1999). Crystal structure of cardosin A, a glycosylated and Arg-Gly-Asp containing aspartic proteinase from the flowers of Cynara cardunculus L. The Journal of Biological Chemistry, 274(39), 27694–27701.

    Google Scholar 

  • Galan, E., Prados, F., Pino, A., Tejada, L., & Fernandez-Salguero, J. (2008). Influence of different amounts of vegetable coagulant from cardoon Cynara cardunculus and calf rennet on the proteolysis and sensory characteristics of cheeses made with sheep milk. International Dairy Journal, 18(1), 93–98.

    CAS  Google Scholar 

  • Garg, G. K., & Virupaks, T. K. (1970). Acid protease from germinated Sorghum. 1. Purification and characterization of enzyme. European Journal of Biochemistry, 17(1), 4–12.

    CAS  Google Scholar 

  • Gildberg, A. (1994). Enzymic processing of marine raw materials. Process Biochemistry, 28(1), 1–15.

    Google Scholar 

  • Gilmartin, L., & Jervis, L. (2002). Production of cod (Gadus morhua) muscle hydrolysates. Influence of combinations of commercial enzyme preparations on hydrolysate peptide size range. Journal of Agricultural and Food Chemistry, 50(19), 5417–5423.

    CAS  Google Scholar 

  • Glathe, S., Kervinen, J., Nimtz, M., Li, G. H., Tobin, G. J., & Copeland, T. D. (1998). Transport and activation of the vacuolar aspartic proteinase phytepsin in barley (Hordeum vulgare L.). The Journal of Biological Chemistry, 273(47), 31230–31236.

    CAS  Google Scholar 

  • Grudkowska, M., & Zagdańska, B. (2004). Multifunctional role of plant cysteine proteinases. Acta Biochimica Polonica, 51(3), 609–624.

    CAS  Google Scholar 

  • Guevara, M. G., Almeida, C., Mendieta, J. R., Faro, C. J., Veríssimo, P., Pires, E. V., et al. (2005). Molecular cloning of a potato leaf cDNA encoding an aspartic protease (StAsp) and its expression after P. infestans infection. Plant Physiology and Biochemistry, 43(9), 882–889.

    CAS  Google Scholar 

  • Guevara, M. G., Daleo, G. R., & Oliva, C. R. (2001). Purification and characterization of an aspartic protease from potato leaves. Physiologia Plantarum, 112(3), 321–326.

    CAS  Google Scholar 

  • Guevara, M. G., Oliva, C. R., Huarte, M., & Daleo, G. R. (2002). An aspartic protease with antimicrobial activity is induced after infection and wounding in intercellular fluids of potato tubers. European Journal of Plant Pathology, 108(2), 131–137.

    CAS  Google Scholar 

  • Guilloteau, M., Laloi, M., Michaux, S., Bucheli, P., & McCarthy, J. (2005). Identification and characterization of the major aspartic proteinase activity in Theobroma cacao seeds. Journal of the Science of Food and Agriculture, 85(4), 549–562.

    CAS  Google Scholar 

  • Gupta, P., Maqbool, T., & Saleemuddin, M. (2007). Oriented immobilization of stem bromelain via the lone histidine on a metal affinity support. Journal of Molecular Catalysis. B, Enzymatic, 45(3–4), 78–83.

    CAS  Google Scholar 

  • Gutiérrez-González, L. H., Rojo-Domínguez, A., Cabrera-González, N. E., Pérez-Montfort, R., & Padilla-Zúñiga, A. J. (2006). Loosely packed papain prosegment displays inhibitory activity. Archives of Biochemistry and Biophysics, 446(2), 151–160.

    Google Scholar 

  • Hale, M. B. (1969). Relative activities of commercially available enzymes in the hydrolysis of fish proteins. Food Technology, 23, 107–110.

    CAS  Google Scholar 

  • Hammond, J. A., Fielding, D., & Bishop, S. C. (1997). Prospects for plant anthelmintics in tropical veterinary medicine. Veterinary Research Communications, 21(3), 213–228.

    CAS  Google Scholar 

  • Hamsher, J.F. & Tate, G.B.E. (1973) Chemically modified proteolytic enzymes. United States Patent N° 3.770.587.

  • Harrach, T., Eckert, K., Maurer, H. R., Machleidt, I., Machleidt, W., & Nuck, R. (1998). Isolation and characterization of two forms of an acidic bromelain stem proteinase. Journal of Protein Chemistry, 17(4), 351–361.

    CAS  Google Scholar 

  • Harrach, T., Eckert, K., Schulze-Forster, K., Nuck, R., Grunow, D., & Maurer, H. R. (1995). Isolation and partial characterization of basic proteinases from stem bromelain. Journal of Protein Chemistry, 14(1), 41–52.

    CAS  Google Scholar 

  • Hartley, B. S. (1960). Proteolytic enzymes. Annual Review of Biochemistry, 29, 45–72.

    CAS  Google Scholar 

  • Heimgartner, U., Pietrzak, M., Geertsen, R., Brodelius, P., Figueiredo, A. C. D., & Pais, M. S. S. (1990). Purification and partial characterization of milk clotting proteases from flowers of Cynara cardunculus. Phytochemistry, 29(5), 1405–1410.

    CAS  Google Scholar 

  • Homaei, A. A., Sajedi, R. H., Sariri, R., Seyfzadeh, S., & Stevanato, R. (2010). Cysteine enhances activity and stability of immobilized papain. Amino Acids, 38(3), 937–942.

    CAS  Google Scholar 

  • Hordegen, P., Cabaret, J., Hertzberg, H., Langhans, W., & Maurer, V. (2006). In vitro screening of six anthelmintic plant products against larval Haemonchus contortus with a modified methyl-thiazolyl-tetrazolium reduction assay. Journal of Ethnopharmacology, 108(1), 85–89.

    CAS  Google Scholar 

  • Hordegen, P., Hertzberg, H., Heilmann, J., Langhans, W., & Maurer, V. (2003). The anthelmintic efficacy of five plant products against gastrointestinal trichostrongylids in artificially infected lambs. Veterinary Parasitology, 117(1–2), 51–60.

    CAS  Google Scholar 

  • Horn, S. J., Aspmo, S. I., & Eijsink, V. G. H. (2005). Growth of Lactobacillus plantarum in media containing hydrolysates of fish viscera. Journal of Applied Microbiology, 99(5), 1082–1089.

    CAS  Google Scholar 

  • Hoyle, N., & Merritt, J. H. (1994). Quality of fish protein hydrolysates from herring (Clupea harengus). Journal of Food Science, 59(1), 76–79.

    CAS  Google Scholar 

  • Huang, D.-J., Chen, H.-J., Hou, W.-C., Chen, T.-E., Hsu, W.-Y., & Lin, Y.-H. (2005). Expression and function of a cysteine proteinase cDNA from sweet potato (Ipomoea batatas [L.] Lam ’Tainong 57′) storage roots. Plant Science, 169(2), 423–431.

    CAS  Google Scholar 

  • Huettner, J. E., & Baughman, R. W. (1986). Primary culture of identified neurons from the visual cortex of postnatal rats. The Journal of Neuroscience, 6(10), 3044–3060.

    CAS  Google Scholar 

  • Husain, S. S., & Lowe, G. (1970). A reinvestigation of residues 64–68 and 175 in papain. Evidence that residues 64 and 175 are asparagine. The Biochemical Journal, 116(4), 689–692.

    CAS  Google Scholar 

  • Ikeuchi, Y., Katerelos, N. A., & Goodenough, P. W. (1998). The enhancing of a cysteine proteinase activity at acidic pH by protein engineering, the role of glutamic 50 in the enzyme mechanism of caricain. FEBS Letters, 437(1–2), 91–96.

    CAS  Google Scholar 

  • Jacquet, A., Kleinschmidt, T., Schnek, A. G., Looze, Y., & Braunitzer, G. (1989). The thiol proteinases from the latex of Carica papaya L. III. The primary structure of chymopapain. Biological Chemistry Hoppe-Seyler, 370(5), 425–434.

    CAS  Google Scholar 

  • James, M. N. G. (2004). Catalytic pathway of aspartic peptidases. In A. J. Barrett, N. D. Rawlings, & J. F. Woessner (Eds.), Handbook of Proteolytic Enzymes. New York: Academic.

    Google Scholar 

  • Jansen, E. F., & Balls, A. K. (1941). Chymopapain: new crystal- line proteins from papaya latex. The Journal of Biological Chemistry, 137, 459–460.

    CAS  Google Scholar 

  • Jin, F., & Toda, K. (1988). Preparation of immobilized papain covalently bound on natural cellulose for treatment of beer. Biotechnology Letters, 10(3), 221–223.

    CAS  Google Scholar 

  • Johnston, R. B. (1956). Thiolesterase activity of papain. The Journal of Biological Chemistry, 221(2), 1037–1046.

    CAS  Google Scholar 

  • Jones, B. L. (2005). Endoproteases of barley and malt. Journal of Cereal Science, 42(2), 139–156.

    CAS  Google Scholar 

  • Jones, I. K., & Glazer, A. N. (1970). Comparative studies on four sulfhydryl endopeptidases (“Ficins”) of Ficus glabrata latex. The Journal of Biological Chemistry, 245, 2765–2772.

    CAS  Google Scholar 

  • Jung, Y., Choi, C., Park, J., Kang, H., Choi, J., Nou, I., et al. (2008). Overexpression of the pineapple fruit bromelain gene (BAA) in transgenic Chinese cabbage (Brassica rapa) results in enhanced resistance to bacterial soft rot. Electronic Journal of Biotechnology, 11(1), 1–9.

    CAS  Google Scholar 

  • Kamphuis, I. G., Kalk, K. H., Swarte, M. B., & Drenth, J. (1984). Structure of papain refined at 1.65 A resolution. Journal of Molecular Biology, 179(2), 233–256.

    CAS  Google Scholar 

  • Kaneda, M., & Tominaga, N. (1975). Isolation and characterization of a proteinase from the sarcocarp of melon fruit. Journal of Biochemistry, 78(6), 1287–1296.

    CAS  Google Scholar 

  • Kennedy, J. F., & Pike, V. W. (1981). Papain, chymotrypsin and related proteins—a comparative study of their beer chill-proofing abilities and characteristics. Enzyme and Microbial Technology, 3(1), 59–63.

    CAS  Google Scholar 

  • Khaparde, S. S., & Singhal, R. S. (2001). Chemically modified papain for applications in detergent formulations. Bioresource Technology, 78(1), 1–4.

    CAS  Google Scholar 

  • Khouri, H. E., Vernet, T., Ménard, R., Parlati, F., Laflamme, P., Tessier, D. C., et al. (1991). Engineering of papain: selective alteration of substrate specificity by site-directed mutagenesis. Biochemistry, 30(37), 8929–8936.

    CAS  Google Scholar 

  • Kim, M., Hamilton, S. E., Guddat, L. W., & Overall, C. M. (2007). Plant collagenase: unique collagenolytic activity of cysteine proteases from ginger. Biochimica et Biophysica Acta: General Subjects, 1770(12), 1627–1635.

    CAS  Google Scholar 

  • Kinoshita, K., Sato, K., Hori, M., Ozaki, H., & Karaki, H. (2003). Decrease in activity of smooth muscle L-type Ca2+ channels and its reversal by NF-kappaB inhibitors in Crohn’s colitis model. American Journal of Physiology. Gastrointestinal and Liver Physiology, 285(3), G483–G493.

    CAS  Google Scholar 

  • Klompong, V., Benjakul, S., Kantachote, D., & Shahidi, F. (2010). Use of protein hydrolysate from yellow stripe trevally (Selaroides leptolepis) as microbial media. Food and Bioprocess Technology. doi:10.1007/s11947-010-0402-9.

    Google Scholar 

  • Kobayashi, T., Kobayashi, E., Sato, S., Hotta, Y., Miyajima, N., Tanaka, A., et al. (1994). Characterization of cDNAs induced in meiotic prophase in lily microsporocytes. DNA Research, 1(1), 15–26.

    CAS  Google Scholar 

  • Kosaka, R. (1995) Detergents with high detergency even at low or high temperature. Jpn. Kokai Tokkyo Koho JP07 82, p. 597

    Google Scholar 

  • Kosaka, R. (1995) Bath preparations containing papain and organic acids. Jpn. Kokai Tokkyo Koho 7 82, p. 138

    Google Scholar 

  • Kotb, R. M., Abdella, A. A., El Kateb, M. A., & Ahmed, A. M. (2010). Clinical evaluation of Papacarie in primary teeth. The Journal of Clinical Pediatric Dentistry, 34(2), 117–123.

    Google Scholar 

  • Kramer, D. E., & Whitaker, J. R. (1969). Multiple molecular forms of ficin—evidence against autolysis as explanation. Plant Physiology, 44(11), 1560–1565.

    CAS  Google Scholar 

  • Kristinsson, H. G., & Rasco, B. A. (2000). Fish protein hydrolysates: production, biochemical, and functional properties. Critical Reviews in Food Science and Nutrition, 40(1), 43–81.

    CAS  Google Scholar 

  • Kuwabara, T., & Suzuki, K. (1995). Reversible changes in conformation of the 23-kDa protein of photosystem-II and their relationship to the susceptibility of the protein to a proteinase from photosystem-II membranes. Plant & Cell Physiology, 36(3), 495–504.

    CAS  Google Scholar 

  • Lang, A., Hatscher, C., Wiegert, C., & Kuhl, P. (2009). Protease-catalysed coupling of N-protected amino acids and peptides with 4-aminoantipyrine. Amino Acids, 36(2), 333–340.

    CAS  Google Scholar 

  • Lawers, A., & Dekeyser, M. P. (1997). The cysteine proteases from the latex of Carica papaya L. In A. Lauwers & S. Scharpe (Eds.), Pharmaceutical Enzymes (pp. 107–131). New York: Marcel Dekker.

    Google Scholar 

  • Lee, K. L., Albee, K. L., Bernasconi, R. J., & Edmunds, T. (1997). Complete amino acid sequence of ananain and a comparison with stem bromelain and other plant cysteine proteases. The Biochemical Journal, 327(1), 199–202.

    CAS  Google Scholar 

  • Lei, H., Wang, W., Chen, L.-L., Li, X.-C., Yi, B., & Deng, L. (2004). The preparation and catalytically active characterization of papain immobilized on magnetic composite microspheres. Enzyme and Microbial Technology, 35(1), 15–21.

    CAS  Google Scholar 

  • Li, F.-Y., Xing, Y.-J., & Ding, X. (2007). Immobilization of papain on cotton fabric by sol-gel method. Enzyme and Microbial Technology, 40(7), 1692–1697.

    CAS  Google Scholar 

  • Liener, I. E. & Friedenson, B. (1970) Ficin. In G. E. Perlmann and L. Lorand (eds) Methods in Enzymology. New York: Academic, vol 19, pp 261–273.

  • Lo Piero, A. R., & Petrone, G. (1999). Purification and partial characterization of an ATP-hydrolyzing serine protease from lettuce leaves. Phytochemistry, 51(3), 349–356.

    Google Scholar 

  • Lo Piero, A. R., Puglisi, I., & Petrone, G. (2002). Characterization of “Lettucine”, a serine-like protease from Lactuca sativa leaves, as a novel enzyme for milk clotting. Journal of Agricultural and Food Chemistry, 50(8), 2439–2443.

    CAS  Google Scholar 

  • Lopes, M. C., Mascarini, R. C., da Silva, B. M., Flório, F. M., & Basting, R. T. (2007). Effect of a papain-based gel for chemomechanical caries removal on dentin shear bond strength. Journal of Dentistry for Children, 74(2), 93–97.

    Google Scholar 

  • Lopez, L. M., Sequeiros, C., Natalucci, C. L., Brullo, A., Maras, B., Barra, D., et al. (2000). Purification and characterization of macrodontain I, a cysteine peptidase from unripe fruits of Pseudananas macrodontes (Morr.) Harms (Bromeliaceae). Protein Expression and Purification, 18(2), 133–140.

    CAS  Google Scholar 

  • Lotz-Winter, H. (1990). On the pharmacology of bromelain: an update with special regard to animal studies on dose-dependent effects. Planta Medica, 56(3), 249–253.

    CAS  Google Scholar 

  • Lown, J. A., & Dale, B. J. (1995). Application of the proteolytic enzyme papain in routine platelet serology. Immunohematology, 11(4), 140–142.

    CAS  Google Scholar 

  • Lynn, K. R., & Yaguchi, M. (1979). N-terminal homology in three cysteinyl proteases from Papaya latex. Biochimica et Biophysica Acta, 581(2), 363–364.

    CAS  Google Scholar 

  • Malthouse, J. P., & Brocklehurst, K. (1976). Preparation of fully active ficin from Ficus glabrata by covalent chromatography and characterization of its active centre by using 2, 2′-depyridyl disulphide as a reactivity probe. The Biochemical Journal, 159(2), 221–234.

    CAS  Google Scholar 

  • Mariani, M., Camagna, M., Tarditi, L., & Seccamani, E. (1991). A new enzymatic method to obtain high yield F(ab’) mouse IgG1. Molecular Immunology, 28(1–2), 69–77.

    CAS  Google Scholar 

  • Martínez, D. E., Bartoli, C. G., Grbic, V., & Guiamet, J. J. (2007). Vacuolar cysteine proteases of wheat (Triticumaestivum L.) are common to leaf senescence induced by different factors. Journal of Experimental Botany, 58(5), 1099–1107.

    Google Scholar 

  • Maurer, H. R. (2001). Review: Bromelain: biochemistry, pharmacology and medical use. Cellular and Molecular Life Science, 58(9), 1234–1245.

    CAS  Google Scholar 

  • Ménard, R., Carriere, J., Laflamme, P., Plouffe, C., Khouri, H. E., Vernet, T., et al. (1991). Contribution of the glutamine 19 side chain to transition-state stabilization in the oxyanion hole of papain. Biochemistry, 30(37), 8924–8928.

    Google Scholar 

  • Ménard, R., Khouri, H. E., Plouffe, C., Dupras, R., Ripoll, D., Vernet, T., et al. (1990). A protein engineering study of the role of aspartate 158 in the catalytic mechanism of papain. Biochemistry, 29(28), 6706–6713.

    Google Scholar 

  • Ménard, R., Plouffe, C., Laflamme, P., Vernet, T., Tessier, D. C., Thomas, D. Y., et al. (1995). Modification of the electrostatic environment is tolerated in the oxyanion hole of the cysteine protease papain. Biochemistry, 34, 464–471.

    Google Scholar 

  • Mendieta, J. R., Pagano, M. R., Muñoz, F. F., Daleo, G. R., & Guevara, M. G. (2006). Antimicrobial activity of potato aspartic proteases (StAPs) involves membrane permeabilization. Microbiology, 152(Pt 7), 2039–2047.

    CAS  Google Scholar 

  • Miller, M. F., Carr, M. A., Ramsey, C. B., Crockett, K. L., & Hoover, L. C. (2001). Consumer thresholds for establishing the value of beef tenderness. Journal of Animal Science, 79(12), 3062–3068.

    CAS  Google Scholar 

  • Mitchel, R. E. J., Chaiken, I. M., & Smith, E. (1970). The complete amino acid sequence of papain. Additions and corrections. The Journal of Biological Chemistry, 245(14), 3485–3492.

    CAS  Google Scholar 

  • Morcelle, S. R., Liggieri, C. S., Bruno, M. A., Priolo, N., & Clapés, P. (2009). Screening of plant peptidases for the synthesis of arginine-based surfactants. Journal of Molecular Catalysis. B, Enzymatic, 57(4), 177–182.

    CAS  Google Scholar 

  • Moutim, V., Silva, L. G., Lopes, M. T. P., Wilson Fernandes, G., & Salas, C. E. (1999). Spontaneous processing of peptides during coagulation of latex from Carica papaya. Plant Science, 142(2), 115–121.

    CAS  Google Scholar 

  • Mueller, M. S., & Mechler, E. (2005). Medicinal plants in tropical countries. Traditional use—Experience-facts. Stuttgart: Thieme.

    Google Scholar 

  • Muñoz, F. F., Mendieta, J. R., Pagano, M. R., Paggi, R. A., Daleo, G. R., & Guevara, M. G. (2010). The swaposin-like domain of potato aspartic protease (StAsp-PSI) exerts antimicrobial activity on plant and human pathogens. Peptides, 31(5), 777–785.

    Google Scholar 

  • Muntz, K., Belozersky, M. A., Dunaevsky, Y. E., Schlereth, A., & Tiedemann, J. (2001). Stored proteinases and the initiation of storage protein mobilization in seeds during germination and seedling growth. Journal of Experimental Botany, 52(362), 1741–1752.

    CAS  Google Scholar 

  • Murachi, T., Yasui, M., & Yasuda, Y. (1964). Purification and physical characterization of stem bromelain. Biochemistry, 3(1), 48–55.

    CAS  Google Scholar 

  • Muta, E., Aramaki, H., Takata, Y., Kono, A., Okamoto, Y, & Ota, S. (1993). Cloning and sequencing of fruit bromelain.Submitted (JAN-1993) to the EMBL/GenBank/DDBJ databases.

  • Mutlu, A., & Gal, S. (1999). Plant aspartic proteinases: enzymes on the way to a function. Physiolgia Plantarum, 105(3), 569–576.

    CAS  Google Scholar 

  • Nakano, T., Murakami, S., Shoji, T., Yoshida, S., Yamada, Y., & Sato, F. (1997). A novel protein with DNA binding activity from tobacco chloroplast nucleoids. The Plant Cell, 9(9), 1673–1682.

    CAS  Google Scholar 

  • Napper, A. D., Bennett, S. P., Borowski, M., Holdridge, M. B., Leonard, M. J., Rogers, E. E., et al. (1994). Purification and characterization of multiple forms of the pineapple-stem-derived cysteine proteinases ananain and comosain. The Biochemical Journal, 301(Pt 3), 727–735.

    CAS  Google Scholar 

  • Narai-Kanayama, A., Koshino, H., & Aso, K. (2008). Mass spectrometric and kinetic studies on slow progression of papain-catalyzed polymerization of l-glutamic acid diethyl ester. Biochimica et Biophysica Acta, 1780(6), 881–891.

    CAS  Google Scholar 

  • Naveena, B. M., Mendiratta, S. K., & Anjaneyulu, A. S. R. (2004). Tenderization of buffalo meat using plant proteases from Cucumis trigonus Roxb (Kachri) and Zingiber officinale roscoe (Ginger rhizome). Meat Science, 68(3), 363–369.

    CAS  Google Scholar 

  • Newkirk, M. M., Edmundson, A., Wistar, R., Jr., Klapper, D. G., & Capra, J. D. (1987). A new protocol to digest human IgM with papain that results in homogeneous fab preparations that can be routinely crystallized. Hybridoma, 6(5), 453–460.

    CAS  Google Scholar 

  • Ottmann, C., Rose, R., Huttenlocher, F., Cedzich, A., Hauske, P., Kaiser, M., et al. (2009). Structural basis for Ca2 + -independence and activation by homodimerization of tomato subtilase 3. Proceedings of the National Academy of Sciences of the United States of America, 106(40), 17223–17228.

    CAS  Google Scholar 

  • Pardo, M. F., Lopez, L. M., Canals, F., Aviles, F. X., Natalucci, C. L., & Caffini, N. O. (2000). Purification of balansain I, an endopeptidase unripe fruits of Bromelia balansae Mez (Bromeliaceae). Journal of Agricultural and Food Chemistry, 48(9), 3795–3800.

    CAS  Google Scholar 

  • Park, H., Kusakabe, I., Sakakibara, Y., & Kobayashi, H. (2001). Autoproteolytic processing of aspartic proteinase from sunflower seeds. Bioscience, Biotechnology, and Biochemistry, 65(3), 702–705.

    CAS  Google Scholar 

  • Pickersgill, R. W., Harris, G. W., & Garman, E. (1992). Structure of monoclinic papain at 1.60-A resolution. Acta Crystallographica. Section B, 48, 59–67.

    Google Scholar 

  • Pickersgill, R. W., Rizkallah, P., Harris, G. W., & Goodenough, P. W. (1991). Determination of the structure of papaya protease omega. Acta Crystallographica, B47, 766–771.

    CAS  Google Scholar 

  • Polaina, J., & MacCabe, A. P. (2007). Industrial Enzymes: Structure, Function and Applications. New York: Springer.

    Google Scholar 

  • Popovic, T., Kidric, M., Puizdar, V., & Brzin, J. (1998). Purification and characterization of two cysteine proteinases from Phaseolus vulgaris leaves. Plant Physiology and Biochemistry, 36(9), 637–645.

    CAS  Google Scholar 

  • Priest, F. G., & Stewart, G. G. (2006). Handbook of Brewing (2nd ed.). New York: CRC.

    Google Scholar 

  • Priolo, N., Del Valle, S. M., Arribere, M. C., Lopez, L., & Caffini, N. (2000). Isolation and characterization of a cysteine protease from the latex of Araujia hortorum fruits. Journal of Protein Chemistry, 19(1), 39–49.

    CAS  Google Scholar 

  • Quaglia, G. B., & Orban, E. (1987). Enzymic solubilisation of proteins of sardine (sardina pilchardus) by commercial proteases. Journal of the Science of Food and Agriculture, 38(3), 263–269.

    CAS  Google Scholar 

  • Radlowski, M., Kalinowski, A., Adamczyk, J., Krolikowski, Z., & Bartkowiak, S. (1996). Proteolytic activity in the maize pollen wall. Physiologia Plantarum, 98(1), 172–178.

    CAS  Google Scholar 

  • Rai, R., & Taneja, V. (1998). Papain catalysed hydantoin hydrolysis in the synthesis of amino acids. Biochemical and Biophysical Research Communications, 244(3), 889–892.

    CAS  Google Scholar 

  • Ramalho-Santos, M., Pissarra, J., Veríssimo, P., Pereira, S., Salema, R., Pires, E., et al. (1997). Cardosin A, an abundant aspartic proteinase, accumulates in protein storage vacuoles in the stigmatic papillae of Cynara cardunculus L. Planta, 203(2), 204–212.

    CAS  Google Scholar 

  • Ramjee, M. K., Petithory, J. R., McElver, J., Weber, S. C., & Kirsch, J. F. (1996). A novel yeast expression/secretion system for the recombinant plant thiol endoprotease propapain. Protein Engineering, 9(11), 1055–1061.

    CAS  Google Scholar 

  • Rao, M. B., Tanksale, A. M., Ghatge, M. S., & Deshpande, V. V. (1998). Molecular and biotechnological aspects of microbial proteases. Microbiology and Molecular Biology Reviews, 62(3), 597–635.

    CAS  Google Scholar 

  • Rawlings, N.D. & Barrett, A.J. (1994). Families of cysteine peptidases. In: Methods in Enzymology Vol 244. Academic Press.

  • Rawlings, N. D., Barrett, A. J., & Bateman, A. (1993). Evolutionary families of peptidases. The Biochemical Journal, 290, 205–218.

    CAS  Google Scholar 

  • Rawlings, N. D., Barrett, A. J., & Bateman, A. (2010). MEROPS: the peptidase database. Nucleic Acids Research, 38, D227–D233.

    CAS  Google Scholar 

  • Revell, D. F., Cummings, N. J., Baker, K. C., Collins, M. E., Taylor, M. A., Sumner, I. G., et al. (1993). Nucleotide sequence and expression in Escherichia coli of cDNAs encoding papaya proteinase omega from Carica papaya. Gene, 127(2), 221–225.

    CAS  Google Scholar 

  • Ritchie, A. H., & Mackie, I. M. (1982). Preparation of fish protein hydrolysates. Animal Feed Science and Technology, 7(2), 125–133.

    CAS  Google Scholar 

  • Ritonja, A., Buttle, D. J., Rawlings, N. D., Turk, V., & Barrett, A. J. (1989). Papaya proteinase IV amino acid sequence. FEBS Letters, 258(1), 109–112.

    CAS  Google Scholar 

  • Ritonja, A., Rowan, A. D., Buttle, D. J., Rawlings, N. D., Turk, V., & Barrett, A. J. (1989). Stem bromelain: amino acid sequence and implications for weak binding of cystatin. FEBS Letters, 247(2), 419–424.

    CAS  Google Scholar 

  • Robertson, C.E. & Goodenough, P.W. (1997). Cloning and expression of ananain gene from pineapple. Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases

  • Rodrigo, I., Vera, P., & Conejero, V. (1989). Degradation of tomato pathogenesis-related proteins by an endogenous 37-kDa aspartyl endoproteinase. European Journal of Biochemistry, 184(3), 663–669.

    CAS  Google Scholar 

  • Rodrigo, I., Vera, P., Vanloon, L. C., & Conejero, V. (1991). Degradation of tobacco pathogenesis-related proteins – evidence for conserved mechanisms of degradation of pathogenesis-related proteins in plants. Plant Physiology, 95(2), 616–622.

    CAS  Google Scholar 

  • Rookard, L. E., Edmondson, O., & Greenwell, P. (2009). ABO reverse grouping: effect of varying concentrations of the enzyme bromelain. British Journal of Biomedical Science, 66(2), 93–97.

    CAS  Google Scholar 

  • Rose, R., Schaller, A. & Ottmann, C. (2010). Structural features of plant subtilases. Plant signaling & behavior, Feb 23; 5(2).

    Google Scholar 

  • Roseiro, L., Barbosa, M., Ames, J., & Wilbey, R. (2003). Cheesmaking with vegetable coagulants- the use of Cynara L. for the production of ovine milk cheese. International Journal of Dairy Technology, 56(2), 76–85.

    Google Scholar 

  • Rosenberg, L., Lapid, O., Bogdanov-Berezovsky, A., Glesinger, R., Krieger, Y., Silberstein, E., et al. (2004). Safety and efficacy of a proteolytic enzyme for enzymatic burn débridement: a preliminary report. Burns, 30(8), 843–850.

    Google Scholar 

  • Rowan, A. D., Buttle, D. J., & Barrett, A. J. (1988). Ananain: a novel cysteine proteinase found in pineapple stem. Archives of Biochemistry and Biophysics, 267(1), 262–270.

    CAS  Google Scholar 

  • Rowan, A. D., Buttle, D. J., & Barrett, A. J. (1990). The cysteine proteinases of the pineapple plant. The Biochemical Journal, 266(3), 869–875.

    CAS  Google Scholar 

  • Roy, J. J., Sumi, S., & Sangeetha, K. (2005). Chemical modification and immobilization of papain. Journal of Chemical Technology and Biotechnology, 80(2), 184–188.

    CAS  Google Scholar 

  • Rudenskaya, G. N., Bogacheva, A. M., Preusser, A., Kuznetsova, A. V., Dunaevsky, Y. E., Golovkin, B. N., et al. (1998). Taraxalisin—A serine proteinase from dandelion Taraxacum officinale Webb s.l. FEBS Letters, 437(3), 237–240.

    CAS  Google Scholar 

  • Rudenskaya, G. N., Bogdanova, E. A., Revina, L. P., Golovkin, B. N., & Stepanov, V. M. (1995). Macluralisin—A serine proteinase from fruits of Maclura pomifera (Raf.) Schneid. Planta, 196(1), 174–179.

    CAS  Google Scholar 

  • Safari, R., Motamedzadegan, A., Ovissipour, M., Regenstein, J. M., Gildberg, A., & Rasco, B. (2009). Use of hydrolysates from yellowfin tuna (Thunnus albacares) heads as a complex nitrogen source for lactic acid bacteria. Food and Bioprocess Technology. doi:10.1107/s11947-009-0225-8.

    Google Scholar 

  • Sagher, O., Szabo, T. A., Chenelle, A. G., & Jane, J. A. (1995). Intraoperative chemonucleolysis as an adjunct to lumbar discectomy. Spine, 20(17), 1923–1927.

    CAS  Google Scholar 

  • Salas, C. E., Gomes, M. T. R., Hernandez, M., & Lopes, M. T. P. (2008). Plant cysteine proteinases: evaluation of the pharmacological activity. Phytochemistry, 69(12), 2263–2269.

    CAS  Google Scholar 

  • Salmia, M. A. (1981). Proteinase activities in resting and germinating-seeds of Scots pine, Pinus sylvestris. Physiologia Plantarum, 53(1), 39–47.

    CAS  Google Scholar 

  • Sampaio, P. N., Fortes, A. M., Cabral, J. M., Pais, M. S., & Fonseca, L. P. (2008). Production and characterization of recombinant cyprosin B in Saccharomyces cerevisiae (W303-1A) strain. Journal of Bioscience and Bioengineering, 105(4), 305–312.

    CAS  Google Scholar 

  • Sangeetha, K., & Abraham, T. E. (2006). Chemical modification of papain for use in alkaline medium. Journal of Molecular Catalysis. B, Enzymatic, 38(3–6), 171–177.

    CAS  Google Scholar 

  • Sarkkinen, P., Kalkkinen, N., Tilgmann, C., Siuro, J., Kervinen, J., & Mikola, L. (1992). Aspartic proteinase from barley grains is related to mammalian lysosomal cathepsin-D. Planta, 186(3), 317–323.

    CAS  Google Scholar 

  • Sarmento, A. C., Lopes, H., Oliveira, C. S., Vitorino, R., Samyn, B., Sergeant, K., et al. (2009). Multiplicity of aspartic proteinases from Cynara cardunculus L. Planta, 230(2), 429–439.

    CAS  Google Scholar 

  • Scannell, A. G., Kenneally, P. M., & Arendt, E. K. (2004). Contribution of starter cultures to the proteolytic process of a fermented non-dried whole muscle ham product. International Journal of Food Microbiology, 93(2), 219–230.

    CAS  Google Scholar 

  • Schaller, A. (2004). A cut above the rest: the regulatory function of plant proteases. Planta, 220(2), 183–197.

    CAS  Google Scholar 

  • Sekizaki, H., Toyota, E., Fuchise, T., Zhou, S., Noguchi, Y., & Horita, K. (2008). Application of several types of substrates to ficin-catalyzed peptide synthesis. Amino Acids, 34(1), 149–153.

    CAS  Google Scholar 

  • Sen, D. P., Sripathy, N. V., Lahiry, N. L., Sreenivasan, A., & Subrahmanyan, V. (1962). Fish hydrolysates.I. Rate of hydrolysis of fish flesh withpapain. Food Technology, 16(5), 138–141.

    CAS  Google Scholar 

  • Sermsart, B., Sripochang, S., Suvajeejarun, T., & Kiatfuengfoo, R. (2005). The molluscicidal activities of some Euphorbia milii hybrids against the snail Indoplanorbis exustus. The Southeast Asian Journal of Tropical Medicine and Public Health, 36(Suppl 4), 192–195.

    Google Scholar 

  • Sgarbieri, V. C., Gupte, S. M., Kramer, D. E., & Whitaker, J. R. (1964). Ficus enzymes I. Separation of the proteolytic enzymes of Ficus carica and Ficus glabrata lattices. The Journal of Biological Chemistry, 239, 2170–2177.

    CAS  Google Scholar 

  • Shuren, J. (2008). Topical drug products containing papain; Enforcement action dates. Washington DC: United States Food and Drug Administration, Department of Health and Human Services.

    Google Scholar 

  • Silva, L. G., Carcia, O., Lopes, M. T., & Salas, C. E. (1997). Changes in protein profile during coagulation of latex from Carica papaya. Brazilian Journal of Medical and Biological Research, 30(5), 615–619.

    CAS  Google Scholar 

  • Simmons, J. W., Nordby, E. J., & Hadjipavlou, A. G. (2001). Chemonucleolysis: the state of the art. European Spine Journal, 10(3), 192–202.

    CAS  Google Scholar 

  • Simoes, I., & Faro, C. (2004). Structure and function of plant aspartic proteinases. European Journal of Biochemistry, 271(11), 2067–2075.

    CAS  Google Scholar 

  • Simões, I., Faro, R., Bur, D., & Faro, C. (2007). Characterization of recombinant CDR1, an Arabidopsis aspartic proteinase involved in disease resistance. The Journal of Biological Chemistry, 282(43), 31358–31365.

    Google Scholar 

  • Soares, P.M.S., Calixto, F.C., & Planta, R.J. (2000). Instituto de Ciencia Aplicada e Technologia, assignee. Production by yeast of aspartic proteinases from plant origin. International Patente WO 00/75283A1.

  • Sripathy, N. V., Sen, D. P., Lahiry, N. L., Sreenivasan, A., & Subrahmanyan, V. (1962). Fish hydrolysates. II. Standardization of digestion conditions for preparation of hydroly- sates rich in peptones and proteoses. Food Technology, 16(5), 141–142.

    CAS  Google Scholar 

  • Stepek, G., Buttle, D. J., Duce, I. R., Lowe, A., & Behnke, J. M. (2005). Assessment of the anthelmintic effect of natural plant cysteine proteinases against the gastrointestinal nematode Heligmosomoides polygyrus, in vitro. Parasitology, 130(Pt 2), 203–211.

    CAS  Google Scholar 

  • Stevenson, D. E., & Storer, A. C. (1991). Papain in organic solvents: determination of conditions suitable for biocatalysis and the effect on substrate specificity and inhibition. Biotechnology and Bioengineering, 37(6), 519–527.

    CAS  Google Scholar 

  • Storer, A.C. & Ménard, R. (1994). Catalytic mechanism in papain family of cysteine peptidases. In: Methods in Enzymology Vol 244. Academic Press.

  • Sullivan, G.A., & Calkins, C.R. (2010). Application of exogenous enzymes to beef muscle of high and low-connective tissue. Meat science Mar 27.

  • Sumantha, A., Larroche, C., & Pandey, A. (2006). Microbiology and industrial biotechnology of food-grade proteases: a perspective. Food Technology and Biotechnology, 44(2), 211–220.

    CAS  Google Scholar 

  • Sutoh, K., Kato, H., & Minamikawa, T. (1999). Identification and possible roles of three types of endopeptidase from germinated wheat seeds. Journal of Biochemistry, 126(4), 700–707.

    CAS  Google Scholar 

  • Tai, D. F., Huang, H. Y., & Huang, C. C. (1995). Immobilized ficin catalyzed synthesis of peptides in organic solvent. Bioorganic & Medicinal Chemistry Letters, 5(14), 1475–1478.

    CAS  Google Scholar 

  • Tanabe, S., Arai, S., & Watanabe, M. (1996). Modification of wheat flour with bromelain and baking hypoallergenic bread with added ingredients. Bioscience, Biotechnology, and Biochemistry, 60(8), 1269–1272.

    CAS  Google Scholar 

  • Taylor, M. A. J., Al-Sheikh, M., Revell, D. F., Sumner, I. G., & Connerton, I. F. (1999). cDNA cloning and expression of Carica papaya prochymopapain isoforms in Escherichia coli. Plant Science, 145(1), 41–47.

    CAS  Google Scholar 

  • Taylor, M. A., Baker, K. C., Briggs, G. S., Connerton, I. F., Cummings, N. J., Pratt, K. A., et al. (1995). Recombinant pro-regions from papain and papaya proteinase IV are selective high affinity inhibitors of the mature papaya enzymes. Protein Engineering, 8(1), 59–62.

    CAS  Google Scholar 

  • Taylor, M. A., Baker, K. C., Connerton, I. F., Cummings, N. J., Harris, G. W., Henderson, I. M., et al. (1994). An unequivocal example of cysteine proteinase activity affected by multiple electrostatic interactions. Protein Engineering, 7(10), 1267–1276.

    CAS  Google Scholar 

  • Taylor, M. A., Pratt, K. A., Revell, D. F., Baker, K. C., Sumner, I. G., & Goodenough, P. W. (1992). Active papain renatured and processed from insoluble recombinant propapain expressed in Escherichia coli. Protein Engineering, 5(5), 455–459.

    CAS  Google Scholar 

  • Terp, N., Thomsen, K. K., Svendsen, I., Davy, A., & Simpson, D. J. (2000). Purification and characterization of hordolisin, a subtilisin-like serine endoprotease from barley. Journal of Plant Physiology, 156(4), 468–476.

    CAS  Google Scholar 

  • Thakurta, P. G., Biswas, S., Chakrabarti, C., Sundd, M., Jagannadham, M. V., & Dattagupta, J. K. (2004). Structural basis of the unusual stability and substrate specificity of ervatamin C, a plant cysteine protease from Ervatamia coronaria. Biochemistry, 43(6), 1532–1540.

    CAS  Google Scholar 

  • Theodorou, L. G., Bieth, J. G., & Papamichael, E. M. (2007). The catalytic mode of cysteine proteinases of papain (C1) family. Bioresource Technology, 98(10), 1931–1939.

    CAS  Google Scholar 

  • Theppakorn, T., Kanasawud, P., & Halling, P. J. (2004). Activity of immobilized papain dehydrated by n-propanol in low-water media. Biotechnology Letters, 26(2), 133–136.

    CAS  Google Scholar 

  • Thomson, A. B. R., Keelan, M., Thiesen, A., Clandinin, M. T., Ropeleski, M., & Wild, G. E. (2001). Small bowel review: normal physiology part 1. Digestive Diseases and Sciences, 46(12), 2567–2587.

    CAS  Google Scholar 

  • Tokes, Z. A., Woon, W. C., & Chambers, S. M. (1974). Digestive enzymes secreted by carnivorous plant Nepenthes macferlanei L. Planta, 119(1), 39–46.

    CAS  Google Scholar 

  • Tomar, R., Kumar, R., & Jagannadham, M. V. (2008). A stable serine protease, wrightin, from the latex of the plant Wrightia tinctoria (Roxb.) R. Br.: purification and biochemical properties. Journal of Agricultural and Food Chemistry, 56(4), 1479–1487.

    CAS  Google Scholar 

  • Tornero, P., Conejero, V., & Vera, P. (1996). Primary structure and expression of a pathogen-induced protease (PR-P69) in tomato plants: similarity of functional domains to subtilisin-like endoproteases. Proceedings of the National Academy of Sciences of the United States of America, 93(13), 6332–6337.

    CAS  Google Scholar 

  • Uchikoba, T., & Kaneda, M. (1996). Milk-clotting activity of cucumisin, a plant serine protease from Melon fruit. Applied Biochemistry and Biotechnology, 56(3), 325–330.

    CAS  Google Scholar 

  • Uchikoba, T., Yonezawa, H., & Kaneda, M. (1995). Cleavage specificity of cucumisin, a plant serine protease. Journal of Biochemistry, 117(5), 1126–1130.

    CAS  Google Scholar 

  • Uhlig, H. (1998). Industrial Enzymes and Their Applications (pp. 147–161). Chichester: Wiley.

    Google Scholar 

  • Uyama, H., Fukuoka, T., Komatsu, I., Watanabe, T., & Kobayashi, S. (2002). Protease-catalyzed regioselective polymerization and copolymerization of glutamic acid diethyl ester. Biomacromolecules, 3(2), 318–323.

    CAS  Google Scholar 

  • Van Beckhoven, R. F., Zenting, H. M., Maurer, K. H., Van Solingen, P. & Weiss, A. (1995) Bacillus cellulases and its application for detergents and textile treatment. European Patent. EP 739.

  • Van Der Hoorn, R. A., & Jones, J. D. (2004). The plant proteolytic machinery and its role in defence. Current Opinion in Plant Biology, 7(4), 400–407.

    Google Scholar 

  • Vanhoof, G., & Cooreman. (1997). Bromelain. In A. Lauwers & S. Scharpe (Eds.), Pharmaceutical Enzymes (pp. 131–155). New York: Marcel Dekker.

    Google Scholar 

  • Vega, R. E., & Brennan, J. G. (1988). Enzymic hydrolysis of fish offal without added water. Journal of Food Engineering, 8(3), 201–215.

    Google Scholar 

  • Veríssimo, P., Esteves, C., Faro, C. J., & Pires, E. V. (1995). The vegetable rennet of Cynara cardunculus contains two proteinases with chymosin and pepsin-like specificities. Biotechnology Letters, 17(6), 621–626.

    Google Scholar 

  • Veríssimo, P., Faro, C., Moir, A. J. G., Lin, Y., Tang, J., & Pires, E. (1996). Purification, characterization and partial amino acid sequence of two novel aspartic proteinases from fresh flowers of Cynara cardunculus L. European Journal of Biochemistry, 235(3), 762–768.

    Google Scholar 

  • Vernet, T., Chatellier, J., Tessier, D. C., & Thomas, D. Y. (1993). Expression of functional papain precursor in Saccharomyces cerevisiae: rapid screening of mutants. Protein Engineering, 6(2), 213–219.

    CAS  Google Scholar 

  • Vernet, T., Khouri, H. E., Laflamme, P., Tessier, D. C., Musil, R., Gour-Salin, B. J., et al. (1991). Processing of the papain precursor. Purification of the zymogen and characterization of its mechanism of processing. The Journal of Biological Chemistry, 266(32), 21451–21457.

    CAS  Google Scholar 

  • Vernet, T., Tessier, D. C., Laliberte, F., Dignard, D., & Thomas, D. Y. (1989). The expression in Escherichia coli of a synthetic gene coding for the precursor of papain is prevented by its own putative signal sequence. Gene, 77(2), 229–236.

    CAS  Google Scholar 

  • Versari, A., Ménard, R., & Lortie, R. (2002). Enzymatic hydrolysis of nitrides by an engineered nitrile hydratase (Papain Gln19Glu) in aqueous-organic. Biotechnology and Bioengineering, 79(1), 9–14.

    CAS  Google Scholar 

  • Vieira, M., Pissarra, J., Veríssimo, P., Castanheira, P., Costa, Y., Pires, E., et al. (2001). Molecular cloning and characterization of cDNA encoding cardosin B, an aspartic proteinase accumulating extracellularly in the transmitting tissue of Cynara cardunculus L. Plant Molecular Biology, 45(5), 529–539.

    CAS  Google Scholar 

  • Vincent, J. L., & Brewin, N. J. (2000). Immunolocalization of a cysteine protease in vacuoles, vesicles, and symbiosomes of pea nodule cells. Plant Physiology, 123(2), 521–530.

    CAS  Google Scholar 

  • Visal, S., Taylor, M. A., & Michaud, D. (1998). The proregion of papaya proteinase IV inhibits Colorado potato beetle digestive cysteine proteinases. FEBS Letters, 434(3), 401–405.

    CAS  Google Scholar 

  • Voigt, J., Kamaruddin, S., Heinrichs, H., Wrann, D., Senyuk, V., & Biehl, B. (1995). Developmental stage-dependent variation of the levels of globular storage protein and aspartic endoprotease during ripening and germination of Theobroma cacao L. seeds. Journal of Plant Physiolgy, 145(3), 299–307.

    CAS  Google Scholar 

  • Wallace, R. H. (1922). Vegetable Rennet Nature, 110(2764), 543.

    Google Scholar 

  • Wang, Y. T., Yang, C. Y., Chen, Y. T., Lin, Y., & Shaw, J. F. (2004). Characterization of senescence-associated proteases in postharvest broccoli florets. Plant Physiology and Biochemistry, 42(7–8), 663–670.

    CAS  Google Scholar 

  • Wang, J. S., Zhao, M. M., Zhao, Q. Z., Bao, Y., & Jiang, Y. M. (2007). Characterization of hydrolysates derived from enzymatic hydrolysis of wheat gluten. Journal of Food Science, 72(2), C103–C107.

    CAS  Google Scholar 

  • Wang, J. S., Zhao, M. M., Zhao, Q. Z., & Jiang, Y. M. (2007). Antioxidant properties of papain hydrolysates of wheat gluten in different oxidation systems. Food Chemistry, 101(4), 1658–1663.

    CAS  Google Scholar 

  • Watson, D. C., Yaguchi, M., & Lynn, K. (1990). The amino acid sequence of chymopapain from Carica papaya. The Biochemical Journal, 266(1), 75–81.

    CAS  Google Scholar 

  • Wharton, C. (1974). The structure and mechanism of stem bromelain. Evaluation of the homogeneity of purified stem bromelain, determination of the molecular weight and kinetic analysis of the bromelain-catalysed hydrolysis of N-benzyloxycarbonyl-L-phenylalanyl-L-serine methyl ester. The Biochemical Journal, 143(3), 575–586.

    CAS  Google Scholar 

  • White, P. C., Cordeiro, M. C., Arnold, D., Brodelius, P. E., & Kay, J. (1999). Processing, activity, and inhibition of recombinant cyprosin, an aspartic proteinase from cardoon (Cynara cardunculus). The Journal of Biological Chemistry, 274(24), 16685–16693.

    CAS  Google Scholar 

  • Whitehurst, R. J., & Van Oort, M. (Eds.). (2010). Enzymes in food technology. West Sussex: Wiley-Blackwell.

    Google Scholar 

  • Williams, D. C., & Whitaker, J. R. (1969). Multiple molecular forms of Ficus glabrata Ficin. Their separation and relative physical, chemical, and enzymatic properties. Plant Physiology, 44, 1574–1583.

    CAS  Google Scholar 

  • Xia, Y., Suzuki, H., Borevitz, J., Blount, J., Guo, Z., Patel, K., et al. (2004). An extracellular aspartic protease functions in Arabidopsis disease resistance signaling. The EMBO Journal, 23(4), 980–988.

    CAS  Google Scholar 

  • Xue, Y., Nie, H., Zhu, L., Li, S., & Zhang, H. (2010). Immobilization of modified papain with anhydride groups on activated cotton fabric. Applied Biochemistry and Biotechnology, 160(1), 109–121.

    CAS  Google Scholar 

  • Yadav, S. C., & Jagannadham, M. V. (2008). Physiological changes and molluscicidal effects of crude latex and milin on Biomphalaria glabrata. Chemosphere, 71(7), 1295–1300.

    CAS  Google Scholar 

  • Yadav, S. C., Jagannadham, M. V., & Kundu, S. (2010). Equilibrium unfolding of kinetically stable serine protease milin: the presence of various active and inactive dimeric intermediates. European Biophysics Journal, 39(10), 1385–1396.

    CAS  Google Scholar 

  • Yadav, S. C., Pande, M., & Jagannadham, M. V. (2006). Highly stable glycosylated serine protease from the medicinal plant Euphorbia milii. Phytochemistry, 67(14), 1414–1426.

    CAS  Google Scholar 

  • Yamagata, H., Aizono, Y. & Hirata, A. (2007) DNA sequence regulating plant fruit-specific expression Patent US 7202355.

  • Yamagata, H., Masuzawa, T., Nagaoka, Y., Ohnishi, T., & Iwasaki, T. (1994). Cucumisin, a serine protease from melon fruit, shares structural homology with subtilisin and is generated from a large precursor. The Journal of Biological Chemistry, 269(52), 32725–32731.

    CAS  Google Scholar 

  • Yamagata, H., Yonesu, K., Hirata, A., & Aizono, Y. (2002). TGTCACA motif is a novel cis-regulatory enhancer element involved in fruit-specific expression of the cucumisin gene. The Journal of Biological Chemistry, 277(13), 11582–11590.

    CAS  Google Scholar 

  • Yoshida-Yamamoto, S., Nishimura, S., Okuno, T., Rakuman, M. & Takii, Y. (2010) Efficient DNA Extraction from Nail Clippings Using the Protease Solution from Cucumis melo. Molecular biotechnology, Mar 20, 1073–6085.

  • Zasloff, M. (2002). Antimicrobial peptides of multicellular organisms. Nature, 415(6870), 389–395.

    CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to express their deepest appreciations to Prof. V. Notario from Georgetown University for correcting and styling the English manuscript. They also wish to extend their gratitude to the Xunta de Galicia and the “Ramon Areces Foundation” from Madrid for financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tomás G. Villa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feijoo-Siota, L., Villa, T.G. Native and Biotechnologically Engineered Plant Proteases with Industrial Applications. Food Bioprocess Technol 4, 1066–1088 (2011). https://doi.org/10.1007/s11947-010-0431-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11947-010-0431-4

Keywords

Navigation