Skip to main content

Advertisement

Log in

Microbial aspartic proteases: current and potential applications in industry

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Aspartic proteases are a relatively small group of proteolytic enzymes that are active in acidic environments and are found across all forms of life. Certain microorganisms secrete such proteases as virulence agents and/or in order to break down proteins thereby liberating assimilable sources of nitrogen. Some of the earlier applications of these proteolytic enzymes are found in the manufacturing of cheese where they are used as milk-clotting agents. Over the last decade, they have received tremendous research interest because of their involvement in human diseases. Furthermore, there has also been a growing interest on these enzymes for their applications in several other industries. Recent research suggests in particular that they could be used in the wine industry to prevent the formation of protein haze while preserving the wines’ organoleptic properties. In this mini-review, the properties and mechanisms of action of aspartic proteases are summarized. Thereafter, a brief overview of the industrial applications of this specific class of proteases is provided. The use of aspartic proteases as alternatives to clarifying agents in various beverage industries is mentioned, and the potential applications in the wine industry are thoroughly discussed.

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.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD (1994) Molecular biology of the cell. Garland, New York

    Google Scholar 

  • Andreeva NS, Rumsh LD (2001) Analysis of crystal structures of aspartic proteinases: on the role of amino acid residues adjacent to the catalytic site of pepsin like enzymes. Protein Sci 10:2439–2450

    PubMed  CAS  PubMed Central  Google Scholar 

  • Anelli G (1977) The proteins of musts. Am J Enol Vitic 28:200–203

    CAS  Google Scholar 

  • Anwar A, Saleemuddin M (1998) Alkaline proteases: a review. Bioresource Technol 64:175–183

    CAS  Google Scholar 

  • Aoki W, Kitahara N, Miura N, Morisaka H, Yamamoto Y, Kuroda K, Ueda M (2012) Candida albicans possesses Sap7 as a pepstatin A-insensitive secreted aspartic protease. PLoS ONE 7:e32513

    PubMed  CAS  PubMed Central  Google Scholar 

  • Bamforth CW (1999) Beer haze. J Am Soc Brew Chem 57:81–90

    CAS  Google Scholar 

  • Barrett AJ, Rawlings ND, Woessner JF (2004) Handbook of proteolytic enzymes. Academic, London

    Google Scholar 

  • Batista L, Monteiro S, Loureiro VB, Teixeira AR, Ferreira RB (2009) The complexity of protein haze formation in wines. Food Chem 112:169–177

    CAS  Google Scholar 

  • Bayly FC, Berg HW (1967) Grape and wine proteins of white wine varietals. Am J Enol Vitic 18:18–32

    CAS  Google Scholar 

  • Bell S, Henschke PA (2005) Implications of nitrogen nutrition for grapes, fermentation and wine. In: Blair R, Francis M, Pretorius I (eds) Advances in wine science. The Australian Wine Research Institute, Adelaide, pp 45–91

    Google Scholar 

  • Beynon RJ, Bond JS (1990) Proteolytic enzymes: a practical approach. Oxford University Press, Oxford

    Google Scholar 

  • Bondoc L, Fitzpatrick S (1998) Size distribution analysis of recombinant adenovirus using disc centrifugation. J Ind Microbiol Biotechnol 20:317–322

    CAS  Google Scholar 

  • Borah D, Yadav RNS, Sangra A, Shahin L, Chaubey AK (2012) Production, purification and characterization of nattokinase from Bacillus subtilis from tea garden soil samples of Dibrugarh, Assum. Asian J Pharm Clin Res 3:124–125

    Google Scholar 

  • Boye JI, Alli I, Ismail AA, Gibbs BF, Konishi Y (1995) Factors affecting molecular characteristics of whey protein gelation. Int Dairy J 5:337–353

    CAS  Google Scholar 

  • Brown SL, Stockdale VJ, Pettolino F, Pocock KF, de Barros LM, Williams PJ, Bacic A, Fincher GB, Høj PB, Waters EJ (2007) Reducing haziness in white wine by overexpression of Saccharomyces cerevisiae genes YOL155c and YDR055w. Appl Microbiol Biotechnol 73:1363–1376

    PubMed  CAS  Google Scholar 

  • Byarugaba-Bazirake GW, van Rensburg P, Kyamuhangire W (2013) The influence of commercial enzymes on wine clarification and on the sensory characteristics of wines made from three banana cultivars. Am J Biotechnol Mol Sci 3:41–62

    Google Scholar 

  • Cabanis JC, Cabanis MT, Cheynier V, Teissedre JL (1998) Tables de compositions. In: Flancy C (ed) Fondements scientifiques et technologiques. Lavoisier Tec & Doc, Cachan, pp 318–326

    Google Scholar 

  • Cabello-Pasini A, Victoria-Cota N, Macias-Carranza V, Hernandez-Garibay E, Muniz-Salazar R (2005) Clarification of wines using polysaccharides extracted from seaweeds. Am J Enol Vitic 56:52–59

    CAS  Google Scholar 

  • Carvalho E, Mateus N, Plet B, Pianet I, Dufourc E, De Freitas V (2006) Influence of wine pectic polysaccharides on the interactions between condensed tannins and salivary proteins. J Agric Food Chem 54:8936–8944

    PubMed  CAS  Google Scholar 

  • Cascella M, Micheletti C, Rothlisberger U, Carloni P (2005) Evolutionarily conserved functional mechanics across pepsin-like and retroviral aspartic proteases. J Am Chem Soc 127:3734–3742

    PubMed  CAS  Google Scholar 

  • Chanalia P, Gandhi D, Jodha D, Singh J (2011) Applications of microbial proteases in pharmaceutical industry: an overview. Rev Med Microbiol 22:96–101

    Google Scholar 

  • Cheng SW, Hu HM, Shen SW, Takagi H, Asano M, Tsai YC (1995) Production and characterization of keratinase of a feather-degrading Bacillus licheniformis PWD-1. Biosci Biotechnol Biochem 59:2239–2243

    PubMed  CAS  Google Scholar 

  • Chi EY, Krishnan S, Rodolph TW, Carpenter JF (2003) Physical stability of proteins in aqueous solutions: mechanisms and driving forces in non native protein aggregation. Pharm Res 20:1325–1336

    PubMed  CAS  Google Scholar 

  • Claverie-Martin F, Vega-Hernandez MC (2007) Aspartic proteases in cheese making. In: Poliana J, Maccabe AP (eds) Industrial enzymes. Springer, New York, pp 207–219

    Google Scholar 

  • Coates L, Erskine PT, Wood SP, Myles DA, Cooper JB (2001) A neutron Laue diffraction study of endothiapepsin: implications for the aspartic proteinase mechanism. Biochemistry 40:13149–13157

    PubMed  CAS  Google Scholar 

  • Conterno L, Delfini C (1994) Peptidase activity and the ability of wine yeasts to utilise grape must proteins as sole nitrogen source. J Wine Res 5:113–126

    Google Scholar 

  • Cooper JB (2002) Five atomic resolution structures of endothiapepsin inhibitor complexes: implications for the aspartic proteinase mechanism. J Mol Biol 318:1405–1415

    PubMed  Google Scholar 

  • Craik CS, Page MJ, Madison EL (2011) Protease as therapeutics. Biochem J 435:1–6

    PubMed  CAS  Google Scholar 

  • Cutfield SM, Dodson EJ, Anderson BF, Moody PC, Marshall CJ, Sullivan PA, Cutfield JF (1995) The crystal structure of a major secreted aspartic proteases from Candida albicans in complexes with two inhibitors. Structure 3:1261–1271

    PubMed  CAS  Google Scholar 

  • Dash C, Kulkarni A, Dunn B, Rao M (2003) Aspartic peptidase inhibitors: implications in drug development. Crit Rev Biochem Mol Biol 38:89–119

    PubMed  CAS  Google Scholar 

  • Dawes H, Boyes S, Keene J, Heatherbell D (1994) Protein instability of wines—influence of protein isolelectric point. Am J Enol Vitic 45:319–326

    CAS  Google Scholar 

  • De Bruijn J, Loyola C, Flores A, Hevia F, Melin P, Serra I (2009) Protein stabilisation of Chardonnay wine using trisacryl and bentonite: a comparative study. Int J Food Sci Technol 44:360–366

    Google Scholar 

  • De Viragh PA, Sanglard D, Togni G, Falchetto R, Monod M (1993) Cloning and sequencing of two Candida parapsilosis genes encoding acid proteases. J Gen Microbiol 139:335–342

    PubMed  Google Scholar 

  • Doco T, Vuchot P, Cheynier V, Moutounet M (2003) Structural modification of wine arabinogalactans during aging on lees. Am J Enol Vitic 54:150–157

    CAS  Google Scholar 

  • Dorado J, Field JA, Almendros G, Sierra-Alvarez R (2001) Nitrogen-removal with protease as a method to improve the selective delignification of hemp stemwood by white-rot fungus Bjerkandera sp. strain BOS55. Appl Microbiol Biotechnol 57:205–211

    PubMed  CAS  Google Scholar 

  • Dufrechou M, Sauvage FX, Bach B, Vernhet A (2010) Protein aggregation in white wines: influence of the temperature on aggregation kinetics and mechanisms. J Agric Food Chem 58:10209–10218

    PubMed  CAS  Google Scholar 

  • Dufrechou M, Poncet-Legrand C, Sauvage FX, Vernhet A (2012) Stability of white wine proteins: combined effect of pH, ionic strength, and temperature on their aggregation. J Agric Food Chem 60:1308–1319

    PubMed  CAS  Google Scholar 

  • Dunn BM (2002) Structure and mechanism of the pepsin-like family of aspartic peptidases. Chem Rev 102:4431–4458

    PubMed  CAS  Google Scholar 

  • Dupin IVS, McKinnon BM, Ryan C, Boulay M, Markides AJ, Jones GP, Williams PJ, Waters EJ (2000) Saccharomyces cerevisiae mannoproteins that protect wine from protein haze: their release during fermentation and lees contact and a proposal for their mechanism of action. J Agric Food Chem 48:3098–3105

    PubMed  CAS  Google Scholar 

  • Esteruelas M, Poinsaut P, Sieczkowski N, Manteau S, Fort F, Canals JM, Zamora F (2009) Characterization of natural haze protein in sauvignon white wine. Food Chem 113:28–35

    CAS  Google Scholar 

  • Esteruelas M, Kontoudakis N, Gil M, Fort MF, Canals J, Zamora F (2011) Phenolic compounds present in natural haze protein of Sauvignon white wine. Food Res Int 44:77–83

    CAS  Google Scholar 

  • Fairlie DP, Tyndall JD, Reid RC, Wong AK, Abbenante G, Scanlon MJ, March DR, Bergman DA, Chai CL, Burkett BA (2000) Conformational selection of inhibitors and substrates by proteolytic enzymes: implications for drug design and polypeptide processing. J Med Chem 43:1271–1281

    PubMed  CAS  Google Scholar 

  • Falconer RJ, Marangon M, Van Sluyter SC, Neilson KA, Chan C, Waters EJ (2010) Thermal stability of thaumatin-like protein, chitinase, and invertase isolated from Sauvignon blanc and Semillon juice and their role in haze formation in wine. J Agric Food Chem 58:975–980

    PubMed  CAS  Google Scholar 

  • Fallon K, Bausch K, Noonan J, Huguenel E, Tamburini P (1997) Role of aspartic proteases in disseminated Candida albicans infection in mice. Infect Immun 65:551–556

    PubMed  CAS  PubMed Central  Google Scholar 

  • Farías ME, Manca de Nadra MC (2000) Purification and partial characterization of Oenococcus oeni exoprotease. FEMS Microbiol Lett 185:263–266

    PubMed  Google Scholar 

  • Ferenczy S (1966) Étude des protéines et des substances azotées. Leur évolution au cours des traitements œnologiques. Conditions de la stabilité protéique des vins. Bull de l’OIV 39:1311–1336

    Google Scholar 

  • Ferreira RB, Picarra-Pereira MA, Monteiro S, Loureiro VB, Teixeira AR (2002) The wine proteins. Trends Food Sci Technol 12:230–239

    Google Scholar 

  • Feuillat M (2005) Use of yeasts in Burgundy and in other regions: fermentation and aging on lees. Les XVIIe entretiens scientitiques de Lallemand. Lallemand, La Rioja, pp 27–32

    Google Scholar 

  • Fleet GH (2003) Yeast interactions and wine flavour. Int J Food Microbiol 86:11–22

    PubMed  CAS  Google Scholar 

  • Folio P, Ritt JF, Alexandre H, Remize F (2008) Characterization of EprA, a major extracellular protein of Oenococcus oeni with protease activity. Int J Food Microbiol 127:26–31

    PubMed  CAS  Google Scholar 

  • Francis IL, Sefton MA, Williams PJ (1994) The sensory effects of pre- or post-fermentation thermal processing on Chardonnay and Semillon wines. Am J Enol Vitic 45:243–251

    CAS  Google Scholar 

  • Friedman R, Caflisch A (2010) On the orientation of the catalytic dyad in aspartic proteases. Proteins 78:1575–1582

    PubMed  CAS  Google Scholar 

  • Fujinami S, Fujisawa M (2010) Industrial application of alkliphiles and their enzyme-past, present and future. Environ Technol 31:845–856

    PubMed  CAS  Google Scholar 

  • Fujiwara N, Yamamoto K, Masui A (1991) Utilization of a thermostable alkaline protease from an alkalophilic thermophile for the recovery of silver from used X-ray film. J Ferment Bioeng 72:306–308

    CAS  Google Scholar 

  • Furia TE (1980) Handbook of food additives. CRC Press, Boca Raton

    Google Scholar 

  • Fusek M, Lin XL, Tang J (1990) Enzymatic properties of thermopsin. J Biol Chem 265:1496–1501

    PubMed  CAS  Google Scholar 

  • Gazzola D, Van Sluyter SC, Curioni A, Waters EJ, Marangon M (2012) Roles of proteins, polysaccharides, and phenolics in haze formation in white wine via reconstitution experiments. J Agric Food Chem 60:10666–10673

    PubMed  CAS  Google Scholar 

  • Ghosh AK (2010) Aspartic acid proteases as therapeutic targets. Wiley-VCH, Germany

    Google Scholar 

  • Glenister PR (1975) Beer deposits: a laboratory guide and pictorial atlas for the study of the various particles found in the deposits of beer and ale. Miles Laboratories, Chicago

    Google Scholar 

  • Gomi K, Arikawa K, Kamiya N, Kitamoto K, Kumagai C (1993) Cloning and nucleotide sequence of the acid protease-encoding gene (pepA) from Aspergillus oryzae. Biosci Biotechnol Biochem 57:1095–1100

    PubMed  CAS  Google Scholar 

  • Guilloux-Benatier M, Remize F, Gal L, Guzzo J, Alexandre H (2006) Effects of yeast proteolytic activity on Oenococcus oeni and malolactic fermentation. FEMS Microbiol Lett 263:183–188

    PubMed  CAS  Google Scholar 

  • Gupta R, Beg QK, Lorenz P (2002) Bacterial alkaline proteases: molecular approaches and industrial applications. Appl Microbiol Biotechnol 59:15–32

    PubMed  CAS  Google Scholar 

  • Horikoshi K (1999) Alkaliphiles: some applications of their products for biotechnology. Microbiol Mol Biol Rev 63:735–750

    PubMed  CAS  PubMed Central  Google Scholar 

  • Horiuchi H, Yanai K, Okazaki T, Takagi M, Yano K (1988) Isolation and sequencing of a genomic clone encoding aspartic proteinase of Rhizopus niveus. J Bacteriol 170:272–278

    PubMed  CAS  PubMed Central  Google Scholar 

  • Hsu JC, Heatherbell DA, Flores JH, Watson BT (1987) Heat-unstable proteins in grape juice and wine. II. Characterization and removal by ultrafiltration. Am J Enol Vitic 38:17–22

    CAS  Google Scholar 

  • Israelachvili J (1991) Electrostatic forces between surfaces in liquids. In: Israelachvili J (ed) Intermolecolar and surface forces. Academic, London, pp 213–259

    Google Scholar 

  • Ito T, Sun L, Bevan MA, Crooks RM (2004) Comparison of nanoparticle size and electrophoretic mobility mesurements using a carbon-nanotube-based coulter counter, dynamic light scattering, transmission electron microscopy, and phase analysis light scattering. Langmuir 20:6940–6945

    PubMed  CAS  Google Scholar 

  • Jarai GG, van den Hombergh H, Buxton FB (1994) Cloning and characterization of the pepE gene of Aspergillus niger encoding a new aspartic protease and regulation of pepE and pepC. Gene 145:171–178

    PubMed  CAS  Google Scholar 

  • Kakimori T, Yoshimoto T, Oyama H, Oda N, Gotoh Y, Oda K, Murao S, Tsuru D (1996) Nucleotide sequence of the gene encoding pepstatin-insensitive acid protease B, Scytalidopepsin B of Scytalidium lignicolum. Biosci Biotechnol Biochem 60:1210–1211

    PubMed  CAS  Google Scholar 

  • Kalisz HM (1988) Microbial proteinases. In: Fiechter A (ed) Advances in biochemical engineering/biotechnology, vol 36 (enzyme studies). Springer, Berlin Heidelberg, pp 3–61

  • Kanehisa K (2000) Woven or knit fabrics manufactured using yarn dyed raw silk. US Patent 6,080,689

  • Khan F (2013) New microbial proteases in leather and detergent industries. Inn Res Chem 1:1–6

    Google Scholar 

  • Kim HK, Hoe HS, Suh DS, Kang SC, Hwang C, Kwon ST (1999) Gene structure and expression of the gene from Beauveria basiana encoding bassiasin I, an insect cuticle-degrading serine protease. Biotechnol Lett 21:777–783

    CAS  Google Scholar 

  • Koaze Y, Goi H, Ezawa K, Yamada Y, Hara T (1964) Fungal proteolytic enzymes. Part I. Isolation of two kinds of acid-proteases excreted by Aspergillus niger var. macrosporus. Agr Biol Chem 28:216–223

    CAS  Google Scholar 

  • Kocabiyik S, Ozel H (2007) An extracellular—pepstatin insensitive acid protease produced by Thermoplasma volcanium. Bioresour Technol 98:112–117

    PubMed  CAS  Google Scholar 

  • Kohn WD, Kay CM, Hodges RS (1997) Salt effects on protein stability: two-stranded alphahelical coiled-coils containing inter- or intrahelical ion pairs. J Mol Biol 267:1039–1052

    PubMed  CAS  Google Scholar 

  • Kumar CG, Takagi H (1999) Microbial alkaline proteases: from a bioindustrial viewpoint. Biotechnol Adv 17:561–594

    PubMed  CAS  Google Scholar 

  • Kwon YT, Kim JO, Moon SY, Lee HH, Rho HM (1994) Extracellular alkaline proteases from alkalophilic Vibrio metschnikovii strain RH530. Biotechnol Lett 16:413–418

    CAS  Google Scholar 

  • Lagace LS, Bisson LF (1990) Survey of yeast acid proteases for effectiveness of wine haze reduction. Am J Enol Vitic 41:147–155

    CAS  Google Scholar 

  • Lambrechts MG, Pretorius IS (2000) Yeast and its importance to wine aroma. S Afr J Enol Vitic 21:97–129

    CAS  Google Scholar 

  • Landbo AK, Pinelo M, Vikbjerg A, Let M, Meyer AS (2006) Protease-assisted clarification of black currant juice: synergy with other clarifying agents and effects on the phenol. J Agric Food Chem 54:6554–6563

    PubMed  CAS  Google Scholar 

  • Le Bourse D, Conreux A, Villaume S, Lameiras P, Nuzillard JM, Jeandet P (2011) Quantification of chitinase and thaumatin-like proteins in grape juices and wines. Anal Bioanal Chem 401:1541–1549

    PubMed  Google Scholar 

  • Li J, Chi Z, Liu Z, Yue L, Peng Y, Wang L (2009) Cloning and characterization of a novel aspartic protease gene from marine-derived Metshnikowia reukaufii and its expression in E. coli. Appl Biochem Biotechnol 159:119–132

    PubMed  CAS  Google Scholar 

  • LI J, Peng Y, Wang X, Chi Z (2010) Optimum production and characterization of an acid protease from marine yeast Metschnikowia reukaufii W6b. J Ocean Univ China 4:359–364

    Google Scholar 

  • Li Q, Yi L, Marek P, Iverson BL (2013) Commercial proteases: present and future. FEBS Lett 587:1155–1163

    PubMed  CAS  Google Scholar 

  • Lopez M, Edens L (2005) Effective prevention of chill-haze in beer using an acid proline-specific endoprotease from Aspergillus niger. J Agric Food Chem 53:7944–7949

    PubMed  CAS  Google Scholar 

  • Lucchetta M, Pocock KF, Waters EJ, Marangon M (2013) Use of zirconium dioxide during fermentation as an alternative to protein fining with bentonite for white wines. Am J Enol Vitic 64:400–404

    CAS  Google Scholar 

  • Machalinski C, Pirpignani ML, Marino C, Mantegazza A, de Jimenez-Bonino MB (2006) Structural aspect of Mucor bacilliformis protenase, a new member of the aspartyl proteinse family. J Biotechnol 123:443–452

    PubMed  CAS  Google Scholar 

  • Madala PK, Tyndall JD, Nall T, Fairlie DP (2010) Update 1 of: proteases universally recognize beta strands in their active sites. Chem Rev 110:PR1–PR31

    PubMed  CAS  Google Scholar 

  • Marangon M, Vincenzi S, Lucchetta M, Curioni A (2010) Heating and reduction affect the reaction with tannins of wine protein fractions differing in hydrophobicity. Anal Chim Acta 660:110–118

    PubMed  CAS  Google Scholar 

  • Marangon M, Lucchetta M, Waters EJ (2011a) Protein stabilisation of white wines using zirconium dioxide enclosed in a metallic cage. Aust J Grape Wine Res 17:28–35

    CAS  Google Scholar 

  • Marangon M, Sauvage FX, Waters EJ, Vernhet A (2011b) Effects of ionic strenght and sulfate upon thermal aggregation of grape chitinases and thaumatin-like proteins in a model system. J Agric Food Chem 59:2652–2662

    PubMed  CAS  Google Scholar 

  • Marangon M, Van Sluyter SC, Neilson KA, Chan C, Haynes PA, Waters EJ, Falconer RJ (2011c) Roles of grape thaumatin-like protein and chitinase in white wine haze formation. J Agric Food Chem 59:733–740

    PubMed  CAS  Google Scholar 

  • Marangon M, Van Sluyter SC, Robinson EM, Muhlack RA, Holt HE, Haynes PA, Godden PW, Smith PA, Waters EJ (2012) Degradation of white wine haze proteins by Aspergillopepsin I and II during juice flash pasteurization. Food Chem 135:1157–1165

    PubMed  CAS  Google Scholar 

  • Marchal A, Marullo P, Moine V, Dubourdieu D (2011) Influence of yeast macromolecules on sweetness in dry wines: role of the Saccharomyces cerevisiae protein Hsp12. J Agric Food Chem 59:2004–2010

    PubMed  CAS  Google Scholar 

  • Marciniszyn J, Hartsuck JA, Tang J (1976) Mode of inhibition of acid proteases by pepstatin. J Biol Chem 251:7088–7094

    PubMed  CAS  Google Scholar 

  • Mesquita PR, Piҫarra-Pereira MA, Monteiro S, Loureiro VB, Teixiera AR, Ferreira RB (2001) Effect of wine composition on protein stability. Am J Enol Vitic 52:324–330

    CAS  Google Scholar 

  • Mienda BS, Yahya A, Galadima IA, Shamsir MS (2014) An overview of microbial proteases for industrial applications. Res J Pharm Biol Chem Sci 5:388–396

    Google Scholar 

  • Milewski S, Andruszkiewicz R, Borowski E (1988) Substrate specificity of peptide permeases in Candida albicans. FEMS Microbiol Lett 50:73–78

    CAS  Google Scholar 

  • Monod M, Togni G, Hube B, Sanglard D (1994) Multiplicity of genes encoding secreted aspartic proteinases in Candida species. Mol Microbiol 13:357–368

    PubMed  CAS  Google Scholar 

  • Moralejo FJ, Cardoza RE, Gutierrez S, Lombrana M, Fierro F, Martin JF (2002) Silencing of the aspergillopepsin B (pepB) gene of Aspergillus awamori by antisense RNA expression or protease removal by gene disruption results in a large increase in thaumatin production. Appl Environ Microbiol 68:3550–3559

    PubMed  CAS  PubMed Central  Google Scholar 

  • Moretti RH, Berg HW (1965) Variability among wine to protein clouding. Am J Enol Vitic 16:18–32

    Google Scholar 

  • Mótyán JA, Tóth F, Tözsér J (2013) Research applications of proteolytic enzymes in molecular biology. Biomolecules 3:923–942

    PubMed  PubMed Central  Google Scholar 

  • Naglik JR, Challacombe SJ, Hube B (2003) Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiol Mol Biol Rev 67:400–428

    PubMed  CAS  PubMed Central  Google Scholar 

  • Nakagawa A (1994) Method for cleaning a contact lens. US Patent 5,314,823

  • Navia MA, Fitzgerald PM, McKeever BM, Leu CT, Heimbach JC, Herber WK, Sigal IS, Darke PL, Springer JP (1989) Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1. Nature 337:615–620

    PubMed  CAS  Google Scholar 

  • Neelakantan S, Mohanty AK (1999) Production and use of microbial enzymes for dairy processing. Curr Sci 77:143–148

    CAS  Google Scholar 

  • Northdrop DB (2001) Follow the protons: a low-barrier hydrogen bond unifies the mechanisms of aspartic proteases. Acc Chem Res 34:790–797

    Google Scholar 

  • O’Donnel D, Wang L, Xu J, Ridgway D, Gu T, Moo-Young M (2001) Enhanced heterologous protein production in Aspergillus niger through pH control of extracellular protease activity. Biochem Eng J 8:187–193

    Google Scholar 

  • Oda K, Nakazima T, Terashita T, Suzuki K, Murao S (1987) Purification and properties of an S-PI (Pepstatin Ac)-insensitive carboxyl proteinase from a Xanthomonas sp. Bacterium. Agric Biol Chem 51:3073–3080

    CAS  Google Scholar 

  • Oh HI, Hoff JE, Armstrong GS, Haff LA (1980) Hydrophobic interaction in tannin-protein complexes. J Agric Food Chem 28:394–398

    CAS  Google Scholar 

  • Pashova V, Güell C, López F (2004a) White wine continuous protein stabilization by packed column. J Agric Food Chem 52:1558–1563

    PubMed  CAS  Google Scholar 

  • Pashova V, Güell C, Pueyo E, López-Barajas M, Polo MC, López F (2004b) White wine protein stabilization by continuous process using packed column. Am J Enol Vitic 55:195–198

    CAS  Google Scholar 

  • Pearl LH, Blundell TL (1984) The active site of aspartic proteinases. FEBS Lett 174:96–101

    PubMed  CAS  Google Scholar 

  • Pellerin P, Waters EJ, Brillouet J, Moutounet M (1994) Effet de polysaccharides sur la formation de trouble protéique dans un vin blanc. J Int Sci Vigne Vin 28:213–225

    CAS  Google Scholar 

  • Pichova I, Pavlickova L, Dostal J, Dolejsi E, Hruskova-Heidingsfeldova O, Weber J, Ruml T, Soucek M (2001) Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors. Eur J Biochem 268:2669–2677

    PubMed  CAS  Google Scholar 

  • Pinelo M, Zeuner B, Meyer AS (2010) Juice clarification by protease and pectinase treatments indicates new roles of pectin and protein in cherry juice turbidity. Food Bioprod Proc 88:259–265

    CAS  Google Scholar 

  • Pocock KF, Høj PB, Adams KS, Kwiatkowski MJ, Waters EJ (2003) Combined heat and proteolytic enzyme treatment of white wines reduce haze forming protein content without detrimental effect. Aust J Grape Wine Res 9:56–63

    CAS  Google Scholar 

  • Pocock KF, Alexander GM, Hayasaka Y, Jones PR, Waters EJ (2007) Sulfate—a candidate for the missing essential factor that is required for the formation of protein haze in white wine. J Agric Food Chem 55:1799–1807

    PubMed  CAS  Google Scholar 

  • Powers JR, Nagel CW, Weller K (1988) Protein removal from wine by immobilized grape proanthocyanidins. Am J Enol Vitic 39:117–120

    CAS  Google Scholar 

  • Prescott M, Peek K, Daniel RM (1995) Characterization of a thermostable pepstatin-insensitive acid proteinase from a Bacillus sp. Int J Biochem 27:729–739

    CAS  Google Scholar 

  • Puri S (2001) An alkaline protease from a Bacillus sp.: production and potential applications in detergent formulation and degumming of silk. Dissertation, University of Delhi

  • Radha S, Nithya VJ, Babu R, Himakiran R, Sridevi A, Prasad NBL, Narasimha G (2011) Production and optimization of acid protease by Aspergillus spp under submerged fermentation. Arch Appl Sci Res 3:155–163

    CAS  Google Scholar 

  • Rani K, Rana R, Datt S (2012) Review on latest overview of proteases. Int J Curr Life Sci 2:12–18

    Google Scholar 

  • Rao MB, Tanksale AM, Ghatge MS, Deshpande VV (1998) Molecular and biotechnological aspects of microbial proteases. Microbiol Mol Biol Rev 62:597–635

    PubMed  CAS  PubMed Central  Google Scholar 

  • Rawlings ND, Bateman A (2009) Pepsin homologues in bacteria. BMC Genomics 10:437–448

    PubMed  PubMed Central  Google Scholar 

  • Rawlings ND, Barrett AJ, Bateman A (2009) MEROPS: the peptidase database. Nucleic Acids Res 38(Database issue):D227–D233

    Google Scholar 

  • Record MT, Zhang W, Anderson CF (1998) Analysis of effects of salts and uncharged solutes on protein and nucleic acid equilibria and processes: practical guide to recognizing and interpreting polyelectrolyte effects, Hofmeister effects, and osmotic effects of salts. Adv Protein Chem 51:281–353

    PubMed  CAS  Google Scholar 

  • Reichard U, Eiffert H, Ruchel R (1994) Purification and characterization of an extracellular aspartic proteinase from Aspergillus fumigatus. J Med Vet Mycol 32:427–436

    PubMed  CAS  Google Scholar 

  • Reid VJ, Theron LW, Du Toit M, Divol B (2012) Identification and partial characterization of extracellular aspartic protease genes from Metschnikowia pulcherrima IWBT Y1123 and Candida apicola IWBT Y1384. Appl Environ Microbiol 19:6838–6849

    Google Scholar 

  • Roland A, Vialaret J, Razungles A, Rigou P, Schneider R (2010) Evolution of S-cysteinylated and S-glutathionylated thiol precursors during oxidation of Melon B. and Sauvignon blanc musts. J Agric Food Chem 58:4406–4413

    PubMed  CAS  Google Scholar 

  • Ruchel R (1986) Cleavage of immunoglobulins by pathogenic yeasts of the genus Candida. Microbiol Sci 3:316–319

    PubMed  CAS  Google Scholar 

  • Saeki K, Ozaki K, Kobayashi T, Ito S (2007) Detergent alkaline proteases: enzymatic properties, genes, and crystal structures. J Biosci Bioeng 103:501–508

    PubMed  CAS  Google Scholar 

  • Salazar FN, Achaerandio I, Labbé MA, Güell C, López F (2006) Comparative study of protein stabilisation in white wine using zirconia and bentonite: physiochemical and wine sensory analysis. J Agric Food Chem 54:9955–9958

    PubMed  CAS  Google Scholar 

  • Sandhya C, Sumantha A, Szakacs G, Pandey A (2005) Comparative evaluation of neutral protease production by Aspergillus oryzae in submerged and solid-state fermentation. Process Biochem 40:2689–2694

    CAS  Google Scholar 

  • Sarmento MR, Oliveira JC, Slatner M, Boulton RB (2000a) Influence of instrintic factors on conventional wine protein satbility tests. Food Control 11:423–432

    CAS  Google Scholar 

  • Sarmento MR, Oliveira JC, Boulton RB (2000b) Selection of low swelling materials for protein adsorption in white wines. Int J Food Sci Technol 35:41–47

    CAS  Google Scholar 

  • Sauvage FX, Bach B, Moutounet M, Vernhet A (2010) Proteins in white wines: thermo-sensitivity and differential adsorbtion by bentonite. Food Chem 118:26–34

    CAS  Google Scholar 

  • Saywell LG (1934) Clarification of wine. Ind Eng Chem 26:981–982

    CAS  Google Scholar 

  • Schoen C, Reichard U, Monod M, Kratzin HD, Ruchel R (2002) Molecular cloning of an extracellular aspartic proteinase from Rhizopus microsporus and evidence for its expression during infection. Med Mycol 40:61–71

    PubMed  CAS  Google Scholar 

  • Shallow DA, Barrett-Bee KJ, Payne JW (1991) Evaluation of the dipeptide and oligopeptide permeases of Candida albicans as uptake routes for synthetic anticandidal agents. FEMS Microbiol Lett 70:9–14

    Google Scholar 

  • Shindo S, Kashiwagi Y, Shiinoki S (1998) Sake brewing from liquefied-rice with immobilised fungal mycelia and immobilised yeast cells. J Inst Brew 104:277–281

    Google Scholar 

  • Shivakumar S (2012) Production and characterization of an acid protease from a local Aspergillus sp. by Solid substrate fermentation. Arch Appl Sci Res 4:188–199

    CAS  Google Scholar 

  • Siala R, Sellami-Kamoun A, Hajji M, Abid I, Gharsallah N, Nasri M (2009) Extracellular acid protease from Aspergillus niger I1: purification and charaterization. Afr J Biotechnol 8:4582–4589

    CAS  Google Scholar 

  • Siebert KJ, Carrasco A, Lynn PY (1996) Formation of protein-polyphenol haze in beverages. J Agric Food Chem 44:1997–2005

    CAS  Google Scholar 

  • Sielecki AR, Fujinaga M, Read RJ, James MN (1991) Refined structure of porcine pepsinogen at 1.8 Å resolution. J Mol Biol 219:671–692

    PubMed  CAS  Google Scholar 

  • Sims GK, Wander MM (2002) Proteolytic activity under nitrogen or sulfur limitation. Appl Soil Ecol 568:1–5

    Google Scholar 

  • Somers TC, Ziemelis G (1973) Direct determination of wine proteins. Am J Enol Vitic 24:47–50

    CAS  Google Scholar 

  • Steiner E, Becker T, Gastl M (2010) Turbity and haze formation in beer—insights and overview. J Inst Brew 116:360–368

    CAS  Google Scholar 

  • Steiner E, Gastl M, Becker T (2011) Protein changes during malting and brewing with focus on haze and foam formation: a review. Eur Food Res Technol 233:191–204

    Google Scholar 

  • Sumantha A, Larroche C, Pandey A (2006) Microbiology and industrial biotechnology of food-grade proteases: a perspective. Food Technol Biotechnol 44:221–20

    Google Scholar 

  • Symersky J, Monod M, Foundling SI (1997) High-resolution structure of the extracellular aspartic proteinase from Candida tropicalis yeast. Biochemistry 36:12700–12710

  • Szecsi PB (1992) The aspartic proteases. Scand J Clin Lab Inv 210:5–22

    CAS  Google Scholar 

  • Tello-Solis AR, Hernandez-Arana A (1995) Effect of irreversibility on the thermodynamic characterization of the thermal denaturation of Aspergillus saitoi acid proteinase. Biochem J 311:969–974

    PubMed  CAS  PubMed Central  Google Scholar 

  • Togni G, Sanglard D, Falchetto R, Monod M (1991) Isolation and nucleotide sequence of the extracellular acid protease gene (ACP) from the yeast, Candida tropicalis. FEBS Lett 286:181–185

    PubMed  CAS  Google Scholar 

  • Tonouchi N, Shoun H, Uozumi T, Beppu T (1986) Cloning and sequencing of a gene for Mucor rennin, an aspartate protease from Mucor pusillus. Nucleic Acids Res 14:7557–7568

    PubMed  CAS  PubMed Central  Google Scholar 

  • Tsushima H, Mine H, Kawakami Y, Hyodoh F, Ueki A (1994) Candida albicans aspartic proteinase cleaves and inactivates human epidermal cysteine proteinase inhibitor, cystatin A. Microbiol 1:167–171

    Google Scholar 

  • Tyndall JDA, Nall T, Fairlie DP (2005) Proteases universally recognize β-strands in their active sites. Chem Rev 105:973–1000

    PubMed  CAS  Google Scholar 

  • Umezawa H, Aoyagi T, Morishima H, Matsuaki M, Hamada M (1970) Pepstatin, a new pepsin inhibitor produced by Actinomycetes. J Antibiot 23:259–262

    PubMed  CAS  Google Scholar 

  • Van Kuyk PA, Cheetham BF, Kate ME (2000) Analysis of two Aspergillus nidulans genes encoding extracellular proteases. Fungal Genet Biol 29:201–210

    Google Scholar 

  • Van Oss CJ (1994) Interfacial forces in aqueous media. Dekker, New York

    Google Scholar 

  • Van Sluyter SC, Marangon M, Stranks SD, Neilson KA, Hayasaka Y, Haynes PA, Menz RI, Waters EJ (2009) Two-step purification of pathogenesis-related proteins from grape juice and crystallization of thaumatin-like proteins. J Agric Food Chem 57:11376–11382

    PubMed  Google Scholar 

  • Van Sluyter SC, Warnock NI, Schmidt S, Anderson P, Van Kan JA, Bacic A, Waters EJ (2013) An aspartic acid protease from Botrytis cinerea removes haze forming proteins during white winemaking. J Agric Food Chem 61:9705–9711

    PubMed  Google Scholar 

  • Veerapandian B, Cooper JB, Sali A, Blundell TL, Rosati RL, Dominy BW, Damon DB, Hoover DJ (1992) Direct observation by X-ray analysis of the tetrahedral “intermediate” of aspartic proteinase. Protein Sci 1:322–328

    PubMed  CAS  PubMed Central  Google Scholar 

  • Vincenzi S, Polesani M, Curioni A (2005) Removal of specific protein components by chitin enhances protein stability in a white wine. Am J Enol Vitic 56:246–254

    CAS  Google Scholar 

  • Vincenzi S, Marangon M, Tolin S, Curioni A (2010) Protein evolution in a white wine during the early stages of winemaking and its relations with wine stability. Aust J Grape Wine Res 17:20–27

    Google Scholar 

  • Vishwanatha KS, Appu Rao AG, Singh SA (2009) Characterisation of acid protease expressed from Aspergillus oryzae MTCC 5341. Food Chem 114:402–407

    CAS  Google Scholar 

  • Von Hippel PH, Wong KY (1964) Neutral salts. The generality of their effects on the stability of macromolecular conformations. Science 145:577–580

    Google Scholar 

  • Ward OP, Rao MB, Kulkarni A (2009) Proteases, Production. In: Schaechter M (ed) Encylopedia of microbiology. Elsevier, USA, pp 495–511

    Google Scholar 

  • Waters EJ, Wallace W, Williams PJ (1991) Heat haze characteristic of fractionated wine proteins. Am J Enol Vitic 42:123–127

    CAS  Google Scholar 

  • Waters EJ, Wallace W, Williams PJ (1992) Identification of heat-unstable wine proteins and their resistance to peptidases. J Agric Food Chem 40:1514–1519

    CAS  Google Scholar 

  • Waters EJ, Pellerin P, Brillouet JM (1994a) A Saccharomyces mannoprotein that protects wine from protein haze. Carbohydr Polym 58:43–48

    CAS  Google Scholar 

  • Waters EJ, Pellerin P, Brillouet JM (1994b) A wine arabinogalactan-protein that reduces heat-induced wine protein haze. Biosci Biotechnol Biochem 58:43–48

    PubMed  CAS  Google Scholar 

  • Waters EJ, Peng Z, Pocock KF, Williams PJ (1995) Proteins in white wine, I: procyanidin occurrence in soluble proteins and insoluble protein hazes and its relationship to protein instability. Aust J Grape Wine Res 1:86–93

    CAS  Google Scholar 

  • Waters EJ, Shirley NJ, Williams PJ (1996) Nuisance proteins of wine are grape pathogenesis-related proteins. J Agric Food Chem 44:3–5

    CAS  Google Scholar 

  • Waters EJ, Hayasaka Y, Tattersall DB, Adams KS, Williams PJ (1998) Sequence analysis of grape (Vitis vinifera) berry chitinases that cause haze formation in wines. J Agric Food Chem 46:4950–4957

    CAS  Google Scholar 

  • Waters EJ, Alexander G, Muhlack R, Pocock KF, Colby C, O’Neill BK, Høj PB, Jones P (2005) Preventing protein haze in bottled white wine. Aust J Grape Wine Res 11:215–225

    CAS  Google Scholar 

  • Weetall HH, Zelko JT, Bailey LF (1984) A new method for the stabilization of white wine. Am J Enol Vitic 35:212–215

    CAS  Google Scholar 

  • Yokotsuka K, Nozaki K, Kushida T (1983) Turbidity formation caused by interaction must proteins with wine tannins. J Ferment Technol 61:413–416

    CAS  Google Scholar 

  • Younes B, Cilindre C, Villaume S, Parmentier M, Jeandet P, Vasserot Y (2011) Evidence for an extracellular acid proteolytic activity secreted by living cells of Saccharomyces cerevisiae PIR1: impact on grape proteins. J Agric Food Chem 59:6239–6246

  • Young JW, Wadeson A, Glover DJ, Quincey RV, Butlin MJ, Kamei EA (1996) The extracellular acid protease of Yarrowia lipolytica: sequence and pH-regulated transcription. Microbiol 142:2913–2921

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Benoit Divol.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Theron, L.W., Divol, B. Microbial aspartic proteases: current and potential applications in industry. Appl Microbiol Biotechnol 98, 8853–8868 (2014). https://doi.org/10.1007/s00253-014-6035-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-014-6035-6

Keywords

Navigation