Molecular modification and biotechnological applications of microbial aspartic proteases

References

• Bach E, Sant’Anna V, Daroit DJ, et al. Production, one-step purification, and characterization of a keratinolytic protease from Serratia marcescens P3. Process Biochem. 2012;47(12):2455–2462.
   Web of Science ®Google Scholar
• dos Santos Aguilar JG, Sato HH. Microbial proteases: production and application in obtaining protein hydrolysates. Food Res Int. 2018;103:253–262.
   PubMed Web of Science ®Google Scholar
• Theron LW, Divol B. Microbial aspartic proteases: current and potential applications in industry. Appl Microbiol Biotechnol. 2014;98(21):8853–8868.
   PubMed Web of Science ®Google Scholar
• Clark DP, Pazdernik NJ. Biotechnology. 2nd ed. USA: academic Cell-Press; 2016.
   Google Scholar
• Di Cera E. Serine proteases. IUBMB life. 2009;61(5):510–515.
   PubMed Web of Science ®Google Scholar
• Liu H, Heng J, Wang L, et al. Identification, characterization, and expression analysis of clip-domain serine protease genes in the silkworm, Bombyx mori. Dev Comp Immunol. 2020;105:103584.
   PubMed Web of Science ®Google Scholar
• Jamir K, Ganguly R, Seshagirirao K. ZCPG, a cysteine protease from zingiber montanum rhizome exhibits enhanced anti-inflammatory and acetylcholinesterase inhibition potential. Int J Biol Macromol. 2020;163:2429–2438.
   PubMed Web of Science ®Google Scholar
• Rawlings ND, Barrett AJ. MEROPS: the peptidase database. Nucleic Acids Res. 1999;27(1):325–331.
   PubMed Web of Science ®Google Scholar
• Faro C, Gal S. Aspartic proteinase content of the arabidopsis genome. Curr Protein Pept Sci. 2005;6(6):493–500.
   PubMed Web of Science ®Google Scholar
• Barrett AJ, Woessner JF, Rawlings ND. Handbook of proteolytic enzymes. Vol. 1. California, USA: Elsevier; 2012.
   Google Scholar
• Guo Y, Tu T, Yuan P, et al. High-level expression and characterization of a novel aspartic protease from talaromyces leycettanus JCM12802 and its potential application in juice clarification. Food Chem. 2019;281:197–203.
   PubMed Web of Science ®Google Scholar
• Purushothaman K, Bhat SK, Singh SA, et al. Aspartic protease from Aspergillus Niger: molecular characterization and interaction with pepstatin A. Int J Biol Macromol. 2019;139:199–212.
   PubMed Web of Science ®Google Scholar
• Sun Q, Chen F, Geng F, et al. A novel aspartic protease from rhizomucor miehei expressed in Pichia pastoris and its application on meat tenderization and preparation of turtle peptides. Food Chem. 2018;245:570–577.
   PubMed Web of Science ®Google Scholar
• Yang X, Cong H, Song J, et al. Heterologous expression of an aspartic protease gene from biocontrol fungus trichoderma asperellum in Pichia pastoris. World J Microbiol Biotechnol. 2013;29(11):2087–2094.
   PubMed Web of Science ®Google Scholar
• Yegin S, Fernandez-Lahore M. A thermolabile aspartic proteinase from mucor mucedo DSM 809: gene identification, cloning, and functional expression in Pichia pastoris. Mol Biotechnol. 2013;54(2):661–672.
   PubMed Web of Science ®Google Scholar
• Souza PM, Werneck G, Aliakbarian B, et al. Production, purification and characterization of an aspartic protease from Aspergillus foetidus. Food Chem Toxicol. 2017;109(Pt 2):1103–1110.
   PubMedGoogle Scholar
• Yegin S, Goksungur Y, Fernandez-Lahore M. Purification, structural characterization, and technological properties of an aspartyl proteinase from submerged cultures of mucor mucedo DSM 809. Food Chem. 2012;133(4):1312–1319.
   Web of Science ®Google Scholar
• Wang X, Ma R, Xie X, et al. Thermostability improvement of a talaromyces leycettanus xylanase by rational protein engineering. Sci Rep. 2017;7(1):1–9.
   PubMed Web of Science ®Google Scholar
• You S, Tu T, Zhang L, et al. Improvement of the thermostability and catalytic efficiency of a highly active β-glucanase from talaromyces leycettanus JCM12802 by optimizing residual charge–charge interactions. Biotechnol Biofuels. 2016;9(1):1–12.
   PubMedGoogle Scholar
• Zhang D, Tu T, Wang Y, et al. Improving the catalytic performance of a talaromyces leycettanus α-amylase by changing the linker length. J Agric Food Chem. 2017;65(24):5041–5048.
   PubMed Web of Science ®Google Scholar
• Guo Y, Tu T, Zheng J, et al. Improvement of BsAPA aspartic protease thermostability via autocatalysis-resistant mutation. J Agric Food Chem. 2019;67(37):10505–10512.
   PubMed Web of Science ®Google Scholar
• Guo Y, Tu T, Zheng J, et al. A novel thermostable aspartic protease from talaromyces leycettanus and its specific autocatalytic activation through an intermediate transition state. Appl Microbiol Biotechnol. 2020;104(11):4915–4926.
   PubMed Web of Science ®Google Scholar
• Beckman M, Holsinger RD, Small DH. Heparin activates β-secretase (BACE1) of alzheimer’s disease and increases autocatalysis of the enzyme. Biochemistry. 2006;45(21):6703–6714.
   PubMed Web of Science ®Google Scholar
• Lim L, Senba H, Kimura Y, et al. Influences of N-linked glycosylation on the biochemical properties of aspartic protease from Aspergillus glaucus MA0196. Process Biochem. 2019;79:74–80.
   Web of Science ®Google Scholar
• Xia Y, Ma Z, Qiu M, et al. N-glycosylation shields phytophthora sojae apoplastic effector PsXEG1 from a specific host aspartic protease. Proc Natl Acad Sci U S A. 2020;117(44):27685–27693.
   PubMed Web of Science ®Google Scholar
• Kangwa M, Salgado JAG, Fernandez-Lahore HM. Identification and characterization of N-glycosylation site on a Mucor circinelloides aspartic protease expressed in Pichia pastoris: effect on secretion, activity and thermo-stability. AMB Expr. 2018;8(1):1–13.
   PubMedGoogle Scholar
• Tong L, Zheng J, Wang X, et al. Improvement of thermostability and catalytic efficiency of glucoamylase from talaromyces leycettanus JCM12802 via site-directed mutagenesis to enhance industrial saccharification applications. Biotechnol Biofuels. 2021;14(1):202–209.
   PubMed Web of Science ®Google Scholar
• Oka T, Murakami K, Wakita T, et al. Comparative site‐directed mutagenesis in the catalytic amino acid triad in calicivirus proteases. Microbiol Immunol. 2011;55(2):108–114.
   PubMed Web of Science ®Google Scholar
• Gao X, Liu E, Yin Y, et al. Enhancing activities of salt-tolerant proteases secreted by Aspergillus oryzae using atmospheric and room-temperature plasma mutagenesis. J Agric Food Chem. 2020;68(9):2757–2764.
   PubMed Web of Science ®Google Scholar
• Pearson MS, Jariwala AR, Abbenante G, et al. New tools for NTD vaccines: a case study of quality control assays for product development of the human hookworm vaccine Na-APR-1M74. Hum Vaccin Immunother. 2015;11(5):1251–1257.
   PubMed Web of Science ®Google Scholar
• Khodai-Kalaki M, Aubert DF, Valvano MA. Characterization of the AtsR hybrid sensor kinase phosphorelay pathway and identification of its response regulator in Burkholderia cenocepacia. J Biol Chem. 2013;288(42):30473–30484.
   PubMed Web of Science ®Google Scholar
• MacPherson DJ, Mills CL, Ondrechen MJ, et al. Tri-arginine exosite patch of caspase-6 recruits substrates for hydrolysis. J Biol Chem. 2019;294(1):71–88.
   PubMed Web of Science ®Google Scholar
• Murthy PS, Palakshappa SH, Padela J, et al. Amelioration of cocoa organoleptics using A. oryzae cysteine proteases. LWT-Food Sci Technol. 2020;120:108919.
   Web of Science ®Google Scholar
• Guerra Y, Valiente PA, Berry C, et al. Predicting functional residues of the solanum lycopersicum aspartic protease inhibitor (SLAPI) by combining sequence and structural analysis with molecular docking. J Mol Model. 2012;18(6):2673–2687.
   PubMed Web of Science ®Google Scholar
• Ruback E, Lobo LA, França TCC, et al. Structural analysis of pla protein from the biological warfare agent Yersinia pestis: docking and molecular dynamics of interactions with the mammalian plasminogen system. J Biomol Struct Dyn. 2013;31(5):477–484.
   PubMed Web of Science ®Google Scholar
• Manahan SE. Green chemistry and the ten commandments of sustainability. Carbon. 2006;100(12):011.
   Google Scholar
• Mandujano-González V, Villa-Tanaca L, Anducho-Reyes MA, et al. Secreted fungal aspartic proteases: a review. Rev Iberoam Micol. 2016;33(2):76–82.
   PubMed Web of Science ®Google Scholar
• Sumantha A, Larroche C, Pandey A. Microbiology and industrial biotechnology of food-grade proteases: a perspective. Food Technol Biotechnol. 2006;44(2):211–220.
   Web of Science ®Google Scholar
• Sampaio e Silva TA, Knob A, Tremacoldi CR, et al. Purification and some properties of an extracellular acid protease from Aspergillus clavatus. World J Microbiol Biotechnol. 2011;27(11):2491–2497.
   Web of Science ®Google Scholar
• Li M, Gustchina A, Cruz R, et al. Structure of RC1339/APRc from Rickettsia conorii, a retropepsin-like aspartic protease. Acta Crystallogr D Biol Crystallogr. 2015;71(Pt 10):2109–2118.
   PubMedGoogle Scholar
• Cruz R, Huesgen P, Riley SP, et al. RC1339/APRc from Rickettsia conorii is a novel aspartic protease with properties of retropepsin-like enzymes. PLoS Pathog. 2014;10(8):e1004324.
   PubMed Web of Science ®Google Scholar
• Chen MT, Lu YY, Weng TM. Comparison of milk-clotting activity of proteinase produced by Bacillus subtilis var, natto and rhizopus oligosporus with commercial rennet. Asian Australas. J. Anim. Sci. 2010;23(10):1369–1379.
   Web of Science ®Google Scholar
• An Z, He X, Gao W, et al. Characteristics of miniature cheddar‐type cheese made by microbial rennet from Bacillus amyloliquefaciens: a comparison with commercial calf rennet. J Food Sci. 2014;79(2):M214–M221.
   PubMed Web of Science ®Google Scholar
• Kumar A, Rao M. Biochemical characterization of a low molecular weight aspartic protease inhibitor from thermo-tolerant Bacillus licheniformis: kinetic interactions with pepsin. Biochim Biophys Acta. 2006;1760(12):1845–1856.
   PubMed Web of Science ®Google Scholar
• Meng X, Zhang J, Wu H, et al. Akkermansia muciniphila aspartic protease amuc_1434* inhibits human colorectal cancer LS174T cell viability via TRAIL-mediated apoptosis pathway. IJMS. 2020;21(9):3385.
   Google Scholar
• Jacob M, Jaros D, Rohm H. Recent advances in milk clotting enzymes. Int J Dairy Technol. 2011;64(1):14–33.
   Web of Science ®Google Scholar
• Heredia-Sandoval NG, Valencia-Tapia MY, Calderón de la Barca AM, et al. Microbial proteases in baked goods: modification of gluten and effects on immunogenicity and product quality. Foods. 2016;5(4):59–69.
   PubMedGoogle Scholar
• Nair IC, Jayachandran K. Aspartic proteases in food industry. In: Parameswaran B, Varjani S, Raveendran S, editors. Green bio-processes. Singapore: Springer; 2019. p. 15–30.
   Google Scholar
• Kumar S, Sharma NS, Saharan MR, et al. Extracellular acid protease from rhizopus oryzae: purification and characterization. Process Biochem. 2005;40(5):1701–1705.
   Web of Science ®Google Scholar
• Deng JJ, Huang WQ, Li ZW, et al. Biocontrol activity of recombinant aspartic protease from trichoderma harzianum against pathogenic fungi. Enzyme Microb Technol. 2018;112:35–42.
   PubMed Web of Science ®Google Scholar
• Savino S, Bulgari D, Monti E, et al. Agro-industrial wastes: a substrate for multi-enzymes production by cryphonectria parasitica. Fermentation. 2021;7(4):279.
   Google Scholar
• da Silva RR, de Oliveira LCG, Juliano MA, et al. Biochemical and milk-clotting properties and mapping of catalytic subsites of an extracellular aspartic peptidase from basidiomycete fungus Phanerochaete chrysosporium. Food Chem. 2017;225:45–54.
   PubMed Web of Science ®Google Scholar
• Van Sluyter SC, Warnock NI, Schmidt S, et al. Aspartic acid protease from Botrytis cinerea removes haze-forming proteins during white winemaking. J Agric Food Chem. 2013;61(40):9705–9711.
   PubMed Web of Science ®Google Scholar
• Kryštůfek R, Šácha P, Starková J, et al. Re-emerging aspartic protease targets: examining Cryptococcus neoformans major aspartyl peptidase 1 as a target for antifungal drug discovery. J Med Chem. 2021;64(10):6706–6719.
   PubMed Web of Science ®Google Scholar
• Bernard D, Mehul B, Thomas-Collignon A, et al. Identification and characterization of a novel retroviral-like aspartic protease specifically expressed in human epidermis. J Invest Dermatol. 2005;125(2):278–287.
   PubMed Web of Science ®Google Scholar
• Pettit SC, Everitt LE, Choudhury S, et al. Initial cleavage of the human immunodeficiency virus type 1 GagPol precursor by its activated protease occurs by an intramolecular mechanism. J Virol. 2004;78(16):8477–8485.
   PubMed Web of Science ®Google Scholar
• Li C, Li X, Lu W. Total chemical synthesis of human T‐cell leukemia virus type 1 protease via native chemical ligation. Pept Sci. 2010;94(4):487–494.
   Google Scholar
• Hill J, Phylip LH. Bacterial aspartic proteinases. FEBS Lett. 1997;409(3):357–360.
   PubMed Web of Science ®Google Scholar
• Hajji M, Hmidet N, Jellouli K, et al. Gene cloning and expression of a detergent stable alkaline protease from Aspergillus clavatus ES1. Process Biochem. 2010;45(10):1746–1752.
   Web of Science ®Google Scholar
• Viniegra-González G, Favela-Torres E, Aguilar CN, et al. Advantages of fungal enzyme production in solid state over liquid fermentation systems. Biochem Eng J. 2003;13(2-3):157–167.
   Web of Science ®Google Scholar
• Yegin S, Fernandez-Lahore M, Jose Gama Salgado A, et al. Aspartic proteinases from mucor spp. in cheese manufacturing. Appl Microbiol Biotechnol. 2011;89(4):949–960.
   PubMed Web of Science ®Google Scholar
• Mendieta JR, Pagano MR, Munoz FF, et al. Antimicrobial activity of potato aspartic proteases (StAPs) involves membrane permeabilization. Microbiology (Reading). 2006;152(Pt 7):2039–2047.
   PubMedGoogle Scholar
• Claverie-MartÌn F, Vega-Hernàndez MC. Aspartic proteases used in cheese making. In: Polaina J, MacCabe AP, editors. Industrial enzymes. Dordrecht, Netherlands: Springer; 2007. p. 207–219.
   Google Scholar
• Matsui T, Kinoshita-Ida Y, Hayashi-Kisumi F, et al. Mouse homologue of skin-specific retroviral-like aspartic protease involved in wrinkle formation. J Biol Chem. 2006;281(37):27512–27525.
   PubMed Web of Science ®Google Scholar
• Puente XS, Sánchez LM, Overall CM, et al. Human and mouse proteases: a comparative genomic approach. Nat Rev Genet. 2003;4(7):544–558.
   PubMed Web of Science ®Google Scholar
• Coates L, Erskine PT, Wood SP, et al. A neutron laue diffraction study of endothiapepsin: implications for the aspartic proteinase mechanism. Biochemistry. 2001;40(44):13149–13157.
   PubMed Web of Science ®Google Scholar
• Caldwell TA, Vickery ON, Colburn JD, et al. Conformational dynamics of the membrane enzyme LspA upon antibiotic and substrate binding. Biophys J. 2022;121(11):2078–2083.
   PubMed Web of Science ®Google Scholar
• Loymunkong C, Sittikul P, Songtawee N, et al. Yield improvement and enzymatic dissection of Plasmodium falciparum plasmepsin V. Mol Biochem Parasitol. 2019;231:111188.
   PubMed Web of Science ®Google Scholar
• Balasubramanian N, Toubarro D, Nascimento G, et al. Purification, molecular characterization and gene expression analysis of an aspartic protease (Sc-ASP113) from the nematode Steinernema carpocapsae during the parasitic stage. Mol Biochem Parasitol. 2012;182(1-2):37–44.
   PubMed Web of Science ®Google Scholar
• Gama Salgado JA, Kangwa M, Fernandez-Lahore M. Cloning and expression of an active aspartic proteinase from Mucor circinelloides in Pichia pastoris. BMC Microbiol. 2013;13(1):250.
   PubMedGoogle Scholar
• Liu Y, Yang Q. Cloning and heterologous expression of aspartic protease SA76 related to biocontrol in trichoderma harzianum. FEMS Microbiol Lett. 2007;277(2):173–181.
   PubMed Web of Science ®Google Scholar
• Xiao H, Sinkovits AF, Bryksa BC, et al. Recombinant expression and partial characterization of an active soluble histo-aspartic protease from Plasmodium falciparum. Protein Expr Purif. 2006;49(1):88–94.
   PubMed Web of Science ®Google Scholar
• Takenaka S, Umeda M, Senba H, et al. Heterologous expression and characterisation of the Aspergillus aspartic protease involved in the hydrolysis and decolorisation of red‐pigmented proteins. J Sci Food Agric. 2017;97(1):95–101.
   PubMed Web of Science ®Google Scholar
• Tcherepanova I, Bhattacharyya L, Rubin CS, et al. Aspartic proteases from the nematode Caenorhabditis elegans: structural organization and developmental and cell-specific expression of asp-1. J Biol Chem. 2000;275(34):26359–26369.
   PubMed Web of Science ®Google Scholar
• Phue JN, Lee SJ, Trinh L, et al. Modified Escherichia coli B (BL21), a superior producer of plasmid DNA compared with Escherichia coli K (DH5α). Biotechnol Bioeng. 2008;101(4):831–836.
   PubMed Web of Science ®Google Scholar
• Zhang H, Wang Y, Brunecky R, et al. A swollenin from talaromyces leycettanus JCM12802 enhances cellulase hydrolysis toward various substrates. Front Microbiol. 2021;12:658096.
   PubMed Web of Science ®Google Scholar
• Wang S, Zhang P, Xue Y, et al. Characterization of a novel aspartic protease from rhizomucor miehei expressed in Aspergillus Niger and its application in production of ACE-Inhibitory peptides. Foods. 2021;10(12):2949.
   PubMed Web of Science ®Google Scholar
• Young CL, Britton ZT, Robinson AS. Recombinant protein expression and purification: a comprehensive review of affinity tags and microbial applications. Biotechnol J. 2012;7(5):620–634.
   PubMed Web of Science ®Google Scholar
• Sachdev D, Chirgwin JM. Properties of soluble fusions between mammalian aspartic proteinases and bacterial maltose-binding protein. J Protein Chem. 1999;18(1):127–136.
   PubMedGoogle Scholar
• Vavrová Ľ, Muchová K, Barák I. Comparison of different Bacillus subtilis expression systems. Res Microbiol. 2010;161(9):791–797.
   PubMed Web of Science ®Google Scholar
• Souza C, Guimarães JM, Pereira S, et al. The multifunctionality of expression systems in Bacillus subtilis: emerging devices for the production of recombinant proteins. Exp Biol Med (Maywood). 2021;246(23):2443–2453.
   PubMed Web of Science ®Google Scholar
• Sak-Ubol S, Namvijitr P, Pechsrichuang P, et al. Secretory production of a beta-mannanase and a chitosanase using a Lactobacillus plantarum expression system. Microb Cell Fact. 2016;15(1):1–12.
   PubMedGoogle Scholar
• Zobel S, Kumpfmüller J, Süssmuth RD, et al. Bacillus subtilis as heterologous host for the secretory production of the non-ribosomal cyclodepsipeptide enniatin. Appl Microbiol Biotechnol. 2015;99(2):681–691.
   PubMed Web of Science ®Google Scholar
• Dong H, Zhang D. Current development in genetic engineering strategies of bacillus species. Microbial Cell Fact. 2014;13(1):1–11.
   PubMedGoogle Scholar
• Hirooka K, Tamano A. Bacillus subtilis highly efficient protein expression systems that are chromosomally integrated and controllable by glucose and rhamnose. Biosci Biotechnol Biochem. 2018;82(11):1942–1954.
   PubMed Web of Science ®Google Scholar
• Song Y, Nikoloff JM, Zhan D. Improving protein production on the level of regulation of both expression and secretion pathways in Bacillus subtilis. J Microbiol Biotechnol. 2015;25(7):963–977.
   PubMed Web of Science ®Google Scholar
• Imamura D, Kuwana R, Kroos L, et al. Substrate specificity of SpoIIGA, a signal-transducing aspartic protease in bacilli. J Biochem. 2011;149(6):665–671.
   PubMed Web of Science ®Google Scholar
• Morello E, Bermudez-Humaran L, Llull D, et al. Lactococcus lactis, an efficient cell factory for recombinant protein production and secretion. J Mol Microbiol Biotechnol. 2008;14(1-3):48–58.
   PubMed Web of Science ®Google Scholar
• Krzeslak J, Braun P, Cool RH, et al. Heterologous production of Escherichia coli penicillin G acylase in Pseudomonas aeruginosa. J Biotechnol. 2009;142(3-4):250–258.
   PubMed Web of Science ®Google Scholar
• Huang K-X, Badger M, Haney K, et al. Large scale production of Bacillus thuringiensis PS149B1 insecticidal proteins Cry34Ab1 and Cry35Ab1 from Pseudomonas fluorescens. Protein Expr Purif. 2007;53(2):325–330.
   PubMed Web of Science ®Google Scholar
• Itaya H, Kikuchi Y. Secretion of Streptomyces mobaraensis pro-transglutaminase by coryneform bacteria. Appl Microbiol Biotechnol. 2008;78(4):621–625.
   PubMed Web of Science ®Google Scholar
• Mukhtar H. Biosynthesis of protease from Lactobacillus paracasei: kinetic analysis of fermentation parameters. Ind J Biochem Biophys. 2006;43(6):377–381.
   PubMed Web of Science ®Google Scholar
• Chen R. Bacterial expression systems for recombinant protein production: e. coli and beyond. Biotechnol Adv. 2012;30(5):1102–1107.
   PubMed Web of Science ®Google Scholar
• Gomes AR, Byregowda SM, Veeregowda BM, Institute of Animal Health and Veterinary Biologicals, KVAFSU, Hebbal, Bengaluru-560024, Karnataka, India, et al. An overview of heterologous expression host systems for the production of recombinant proteins. Adv. Anim. Vet. Sci. 2016;4(7):346–356.
   Google Scholar
• Yang S, Kuang Y, Li H, et al. Enhanced production of recombinant secretory proteins in Pichia pastoris by optimizing Kex2 P1’site. PLoS One. 2013;8(9):e75347.
   PubMed Web of Science ®Google Scholar
• Karbalaei M, Rezaee SA, Farsiani H. Pichia pastoris: a highly successful expression system for optimal synthesis of heterologous proteins. J Cell Physiol. 2020;235(9):5867–5881.
   PubMed Web of Science ®Google Scholar
• Guo Y, Li X, Jia W, et al. Characterization of an intracellular aspartic protease (PsAPA) from penicillium sp. XT7 and its application in collagen extraction. Food Chem. 2021;345:128834.
   PubMed Web of Science ®Google Scholar
• Nevalainen H, Peterson R, Curach N. Overview of gene expression using filamentous fungi. Curr Protoc Prot Sci. 2018;92(1):e55.
   PubMedGoogle Scholar
• Schmoll M, Dattenböck C. Gene expression systems in fungi: advancements and applications. Cham, Switzerland: Springer; 2016. p. 309–334.
   Google Scholar
• MacKenzie D, Jeenes D, Archer D. Filamentous fungi as expression systems for heterologous proteins. In: Genetics and biotechnology. Berlin, Heidelberg: Springer; 2004; p. 289–315.
   Google Scholar
• Madhavan A, Pandey A, Sukumaran RK. Expression system for heterologous protein expression in the filamentous fungus Aspergillus unguis. Bioresour Technol. 2017;245(Pt B):1334–1342.
   PubMedGoogle Scholar
• Sandini S, La Valle R, Deaglio S, et al. A highly immunogenic recombinant and truncated protein of the secreted aspartic proteases family (rSap2t) of Candida albicans as a mucosal anticandidal vaccine. FEMS Immunol Med Microbiol. 2011;62(2):215–224.
   PubMedGoogle Scholar
• Long C, Cui J, Zeng B, et al. Screening and identification of anti-glucose repression proteins in cellulase production fungus trichoderma orientalis EU7-22. Int J Agric Biol. 2020;23(2):399–404.
   Web of Science ®Google Scholar
• Long C, Cheng Y, Gan L, et al. Identification of a genomic region containing a novel promoter resistant to glucose repression and over-expression of β-glucosidase gene in hypocrea orientalis EU7-22. Int J Mol Sci. 2013;14(4):8479–8490.
   PubMed Web of Science ®Google Scholar
• Dou K, Wang Z, Zhang R, et al. Cloning and characteristic analysis of a novel aspartic protease gene Asp55 from trichoderma asperellum ACCC30536. Microbiol Res. 2014;169(12):915–923.
   PubMedGoogle Scholar
• Balasubramanian N, Nascimento G, Ferreira R, et al. Pepsin-like aspartic protease (Sc-ASP155) cloning, molecular characterization and gene expression analysis in developmental stages of nematode Steinernema carpocapsae. Gene. 2012;500(2):164–171.
   PubMed Web of Science ®Google Scholar
• Feijoo-Siota L, Rama JLR, Sánchez-Pérez A, et al. Expression, activation and processing of a novel plant milk-clotting aspartic protease in Pichia pastoris. J Biotechnol. 2018;268:28–39.
   PubMed Web of Science ®Google Scholar
• Guo Z-P, Qiu C-y, Zhang L, et al. Expression of aspartic protease from Neurospora crassa in industrial ethanol-producing yeast and its application in ethanol production. Enzyme Microb Technol. 2011;48(2):148–154.
   PubMed Web of Science ®Google Scholar
• Nie Z, Liu P, Wang Y, et al. Directed Evolution and rational design of mechanosensitive channel MscCG2 for improved glutamate excretion efficiency. J Agric Food Chem. 2021;69(51):15660–15669.
   PubMed Web of Science ®Google Scholar
• Aucamp JP, Cosme AM, Lye GJ, et al. High‐throughput measurement of protein stability in microtiter plates. Biotechnol Bioeng. 2005;89(5):599–607.
   PubMed Web of Science ®Google Scholar
• Yu H, Ma S, Li Y, et al. Hot spots-making directed evolution easier. Biotechnol Adv. 2022;56:107926.
   PubMed Web of Science ®Google Scholar
• O'Loughlin TL, Greene DN, Matsumura I. Diversification and specialization of HIV protease function during in vitro evolution. Mol Biol Evol. 2006;23(4):764–772.
   PubMed Web of Science ®Google Scholar
• Hu W, Liu X, Li Y, et al. Rational design for the stability improvement of armillariella tabescens β-mannanase MAN47 based on N-glycosylation modification. Enzyme Microb Technol. 2017;97:82–89.
   PubMed Web of Science ®Google Scholar
• Li H, Turunen O. Effect of acidic amino acids engineered into the active site cleft of Thermopolyspora flexuosa GH11 xylanase. Biotechnol Appl Biochem. 2015;62(4):433–440.
   PubMed Web of Science ®Google Scholar
• Yu X-W, Tan N-J, Xiao R, et al. Engineering a disulfide bond in the lid hinge region of rhizopus chinensis lipase: increased thermostability and altered acyl chain length specificity. PLoS One. 2012;7(10):e46388.
   PubMed Web of Science ®Google Scholar
• Li J-F, Zhao S-G, Tang C-D, et al. Cloning and functional expression of an acidophilic β-mannanase gene (Anman5A) from Aspergillus Niger LW-1 in Pichia pastoris. J Agric Food Chem. 2012;60(3):765–773.
   PubMed Web of Science ®Google Scholar
• Ding H, Gao F, Liu D, et al. Significant improvement of thermal stability of glucose 1-dehydrogenase by introducing disulfide bonds at the tetramer interface. Enzyme Microb Technol. 2013;53(6-7):365–372.
   PubMed Web of Science ®Google Scholar
• Cao H, Nie K, Li C, et al. Rational design of substrate binding pockets in polyphosphate kinase for use in cost-effective ATP-dependent Cascade reactions. Appl Microbiol Biotechnol. 2017;101(13):5325–5332.
   PubMed Web of Science ®Google Scholar
• Yang H, Liu L, Li J, et al. Rational design to improve protein thermostability: recent advances and prospects. ChemBioEng Rev. 2015;2(2):87–94.
   Google Scholar
• Bhakat S, Söderhjelm P. Flap dynamics in pepsin-like aspartic proteases: a computational perspective using Plasmepsin-II and BACE-1 as model systems. J. Chem. Inf. Model. 2022;62(4):914–926.
   PubMed Web of Science ®Google Scholar
• Bjelic S, Åqvist J. Computational prediction of structure, substrate binding mode, mechanism, and rate for a malaria protease with a novel type of active site. Biochemistry. 2004;43(46):14521–14528.
   PubMed Web of Science ®Google Scholar
• Korendovych IV. Rational and semirational protein design. Prot Eng. 2018;1685:15–23.
   Google Scholar
• Nascimento AS, Krauchenco S, Golubev AM, et al. Statistical coupling analysis of aspartic proteinases based on crystal structures of the Trichoderma reesei enzyme and its complex with pepstatin A. J Mol Biol. 2008;382(3):763–778.
   PubMed Web of Science ®Google Scholar
• Fujinaga M, Chernaia MM, Mosimann SC, et al. Crystal structure of human pepsin and its complex with pepstatin. Protein Sci. 1995;4(5):960–972.
   PubMed Web of Science ®Google Scholar
• Ma S, Henderson JA, Shen J. Exploring the pH-Dependent structure–dynamics–function relationship of human renin. J Chem Inf Model. 2021;61(1):400–407.
   PubMed Web of Science ®Google Scholar
• Doukas PG, Vageli DP, Sasaki CT, et al. Pepsin promotes activation of epidermal growth factor receptor and downstream oncogenic pathways, at slightly acidic and neutral pH, in exposed hypopharyngeal cells. IJMS. 2021;22(8):4275.
   Google Scholar
• Bose I, Zhao Y. Selective hydrolysis of aryl esters under acidic and neutral conditions by a synthetic aspartic protease mimic. ACS Catal. 2021;11(7):3938–3942.
   PubMed Web of Science ®Google Scholar
• Suttiprapa S, Mulvenna J, Huong NT, et al. Ov-APR-1, an aspartic protease from the carcinogenic liver fluke, Opisthorchis viverrini: functional expression, immunolocalization and subsite specificity. Int J Biochem Cell Biol. 2009;41(5):1148–1156.
   PubMed Web of Science ®Google Scholar
• Xu J, Liu RD, Bai SJ, et al. Molecular characterization of a Trichinella spiralis aspartic protease and its facilitation role in larval invasion of host intestinal epithelial cells. PLoS Negl Trop Dis. 2020;14(4):e0008269.
   PubMed Web of Science ®Google Scholar
• Aoki W, Kitahara N, Miura N, et al. Candida albicans possesses Sap7 as a pepstatin A-insensitive secreted aspartic protease. PLoS One. 2012;7(2):e32513.
   PubMed Web of Science ®Google Scholar
• Gao B, He L, Wei D, et al. Identification and magnetic immobilization of a pyrophilous aspartic protease from antarctic psychrophilic fungus. J Food Biochem. 2018;42(6):e12691.
   Web of Science ®Google Scholar
• Zou S, Xie L, Liu Y, et al. N-linked glycosylation influences on the catalytic and biochemical properties of penicillium purpurogenum β-d-glucuronidase. J Biotechnol. 2012;157(3):399–404.
   PubMed Web of Science ®Google Scholar
• Wang Z, Guo C, Liu L, et al. Effects of N-glycosylation on the biochemical properties of recombinant bEKL expressed in Pichia pastoris. Enzyme Microb Technol. 2018;114:40–47.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Miao Y, Zhi F, et al. Rational Design of pepsin for enhanced thermostability via exploiting the guide of structural weakness on stability. Front Phys. 2021;9:586.
   Web of Science ®Google Scholar
• Lai Y, Li W, Wu X, et al. A highly efficient protein degradation system in bacillus sp. CN2: a functional-degradomics study. Appl Microbiol Biotechnol. 2021;105(2):707–723.
   PubMed Web of Science ®Google Scholar
• Khan AR, Parrish JC, Fraser ME, et al. Lowering the entropic barrier for binding conformationally flexible inhibitors to enzymes. Biochemistry. 1998;37(48):16839–16845.
   PubMed Web of Science ®Google Scholar
• Shen CH, Wang YF, Kovalevsky AY, et al. Amprenavir complexes with HIV‐1 protease and its drug‐resistant mutants altering hydrophobic clusters. Febs J. 2010;277(18):3699–3714.
   PubMed Web of Science ®Google Scholar
• Theron LW, Bely M, Divol B. Monitoring the impact of an aspartic protease (MpAPr1) on grape proteins and wine properties. Appl Microbiol Biotechnol. 2018;102(12):5173–5183.
   PubMed Web of Science ®Google Scholar
• Siala R, Kamoun A, Hajji M, et al. Extracellular acid protease from Aspergillus Niger I1: purification and characterization. African J Biotechnol. 2009;8(18):4582–4589.
   Google Scholar
• Zhang GQ, Zhang QP, Sun Y, et al. Purification of a novel pepsin inhibitor from coriolus versicolor and its biochemical properties. J Food Sci. 2012;77(3):C293–C297.
   PubMed Web of Science ®Google Scholar
• Vishwanatha K, Rao AA, Singh SA. Characterisation of acid protease expressed from Aspergillus oryzae MTCC 5341. Food Chem. 2009;114(2):402–407.
   Web of Science ®Google Scholar
• Aoki K, Matsubara S, Umeda M, et al. Aspartic protease from Aspergillus (eurotium) repens strain MK82 is involved in the hydrolysis and decolourisation of dried bonito (katsuobushi). J Sci Food Agric. 2013;93(6):1349–1355.
   PubMed Web of Science ®Google Scholar
• Juárez-Montiel M, Tesillo-Moreno P, Cruz-Angeles A, et al. Heterologous expression and characterization of the aspartic endoprotease Pep4um from Ustilago maydis, a homolog of the human chatepsin D, an important breast cancer therapeutic target. Mol Biol Rep. 2018;45(5):1155–1163.
   PubMed Web of Science ®Google Scholar
• Ajith S, Ghosh J, Shet D, et al. Partial purification and characterization of phytase from Aspergillus foetidus MTCC 11682. AMB Express. 2019;9(1):3–11.
   PubMed Web of Science ®Google Scholar
• Mamo J, Kangwa M, Suarez Orellana JF, et al. Purification and characterization of aspartic protease produced from Aspergillus oryzae DRDFS13 MN726447 under Solid-State fermentation. Catal Lett. 2022;152(7):2033–2046.
   Web of Science ®Google Scholar
• Chinmayee C, Martin A, Kumar BG, et al. A new thermostable rhizopuspepsin: purification and biochemical characterisation. Process Biochem. 2022;112:18–26.
   Web of Science ®Google Scholar
• Zeleznik TZ, Puizdar V, Dolenc I. Expression, purification and auto-activation of cathepsin E from insect cells. Protein Pept Lett. 2015;22(6):525–531.
   PubMed Web of Science ®Google Scholar
• Sun F, Sun Q, Zhang H, et al. Purification and biochemical characteristics of the microbial extracellular protease from Lactobacillus curvatus isolated from harbin dry sausages. Int J Biol Macromol. 2019;133:987–997.
   PubMed Web of Science ®Google Scholar
• Li L, Gong J, Wang S, et al. Heterologous expression and characterization of a new clade of aspergillus α-L-rhamnosidase suitable for citrus juice processing. J Agric Food Chem. 2019;67(10):2926–2935.
   PubMed Web of Science ®Google Scholar
• Yin C, Zheng L, Chen L, et al. Cloning, expression, and characterization of a milk-clotting aspartic protease gene (Po-Asp) from Pleurotus ostreatus. Appl Biochem Biotechnol. 2014;172(4):2119–2131.
   PubMed Web of Science ®Google Scholar
• Mahmood W, Viberg LT, Fischer K, et al. An aspartic protease of the scabies mite sarcoptes scabiei is involved in the digestion of host skin and blood macromolecules. PLoS Negl Trop Dis. 2013;7(11):e2525.
   PubMed Web of Science ®Google Scholar
• Kozik A, Gogol M, Bochenska O, et al. Kinin release from human kininogen by 10 aspartic proteases produced by pathogenic yeast Candida albicans. BMC Microbiol. 2015;15(1):1–14.
   PubMedGoogle Scholar
• Wu H, Downs D, Ghosh K, et al. Candida albicans secreted aspartic proteases 4–6 induce apoptosis of epithelial cells by a novel trojan horse mechanism. Faseb J. 2013;27(6):2132–2144.
   PubMed Web of Science ®Google Scholar
• Wasyl K, Zawistowska-Deniziak A, Bąska P, et al. Molecular cloning and expression of the cDNA sequence encoding a novel aspartic protease from uncinaria stenocephala. Exp Parasitol. 2013;134(2):220–227.
   PubMed Web of Science ®Google Scholar
• Zhao G, Song X, Kong X, et al. Immunization with Toxoplasma gondii aspartic protease 3 increases survival time of infected mice. Acta Trop. 2017;171:17–23.
   PubMed Web of Science ®Google Scholar
• Meng X, Wang W, Lan T, et al. A purified aspartic protease from Akkermansia Muciniphila plays an important role in degrading Muc2. IJMS. 2019;21(1):72.
   Google Scholar
• Zawrotniak M, Bochenska O, Karkowska-Kuleta J, et al. Aspartic proteases and major cell wall components in Candida albicans trigger the release of neutrophil extracellular traps. Front Cell Infect Microbiol. 2017;7:414.
   PubMed Web of Science ®Google Scholar
• Hiraishi T. Poly (aspartic acid)(PAA) hydrolases and PAA biodegradation: current knowledge and impact on applications. Appl Microbiol Biotechnol. 2016;100(4):1623–1630.
   PubMed Web of Science ®Google Scholar
• Yang F, Totsingan F, Dolan E, et al. Protease-catalyzed l-aspartate oligomerization: substrate selectivity and computational modeling. ACS Omega. 2020;5(9):4403–4414.
   PubMed Web of Science ®Google Scholar
• Tsuchiya K, Numata K. Facile terminal functionalization of peptides by protease-catalyzed chemoenzymatic polymerization toward synthesis of polymeric architectures consisting of peptides. Polym. Chem. 2020;11(2):560–567.
   Web of Science ®Google Scholar
• Ageitos JM, Yazawa K, Tateishi A, et al. The benzyl ester group of amino acid monomers enhances substrate affinity and broadens the substrate specificity of the enzyme catalyst in chemoenzymatic copolymerization. Biomacromol. 2016;17(1):314–323.
   PubMed Web of Science ®Google Scholar
• Gimenez-Dejoz J, Tsuchiya K, Numata K. Insights into the stereospecificity in papain-mediated chemoenzymatic polymerization from quantum mechanics/molecular mechanics simulations. ACS Chem Biol. 2019;14(6):1280–1292.
   PubMed Web of Science ®Google Scholar