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An up-to-date review of biomedical applications of serratiopeptidase and its biobetter derivatives as a multi-potential metalloprotease

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Abstract

Serratiopeptidase is a bacterial metalloprotease used in a variety of medical applications. The multidimensional properties of serratiopeptidase make it noticeable as a miraculous enzyme. Anti-coagulant, anti-inflammatory and anti-biofilm activity of serratiopeptidase making it useful in reducing pain and swelling associated with various conditions including arthritis, diabetes, cancer, swelling, pain and also thrombolytic disorders. It breaks down fibrin, thins the fluids formed during inflammation and due to its anti-biofilm activity, can be used in the combination of antibiotics to reduce development of antibiotic resistance. However, some drawbacks like sensitivity to environmental conditions and low penetration into cells due to its large size have limited its usage as a potent pharmaceutical agent. To overcome such limitations, improved versions of the enzyme were introduced using protein engineering in our previous studies. Novel functional serratiopeptidases with shorter length and higher stability have seemingly created a hope for using this enzyme as a more effective therapeutic enzyme. This review explains the structural properties and functional aspects of serratiopeptidase, its main characteristics and properties, pre-clinical and clinical applications of the enzyme, improved qualities of the modified forms, different formulations of the enzyme, and the potential future developments.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Aishwarya SS, Selvarajan E, Iyappan S, Rajnish KN (2019) Recombinant l-Asparaginase II from Lactobacillus casei subsp. casei ATCC 393 and Its Anticancer Activity. Indian J Microbiol 59(3):313–320. https://doi.org/10.1007/s12088-019-00806-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ammar A, Samir R, El-Wafa WA, Amin M (2019) The Production of serratiopeptidase and its application as an anti-inflammatory agent in bacterial pneumonia. Egypt J Biotechnol 58:1–16

    Google Scholar 

  • Anil CS, Kashinath MA (2013) Production, characterization and optimization of potent protease (serratiopeptidase) from Serratia marcescens e 15. Int Res J Pharm Appl Sci 3(4):95–98

    Google Scholar 

  • Araghi A, Hashemi S, Sepahi AA, Faramarzi MA, Amin M (2019) Purification and study of anti-cancer effects of Serratia marcescens serralysin. Iranian Journal of Microbiology 11(4):320–327

    PubMed  PubMed Central  Google Scholar 

  • Artini M, Vrenna G, Trecca M, Tuccio Guarna Assanti V, Fiscarelli EV, Papa R, Selan L (2022) Serratiopeptidase affects the physiology of Pseudomonas aeruginosa Isolates from cystic fibrosis patients. Int J Mol Sci 23(20):12645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ateia YA, Al-Edanni MS, Al-Qurtas MI (2018) Impact of metformin and serratiopeptidase in obese patients with knee osteoarthritis. Int J Pharm Pharm Sci 10(2):37–41

    Article  CAS  Google Scholar 

  • Barman S, Bhattacharya SS, Mandal N (2020) Chapter 3 - Serratia. In: Amaresan N, Senthil Kumar M, Annapurna K, Kumar K, Sankaranarayanan A (Eds.) Beneficial Microbes in Agro-Ecology. Academic Press, pp 27–36

  • Bartos D, Daraban A, Badila E, Tintea E, Ene E, Vatasescu R (2014) Biventricular cardiac pacing as a last chance for a patient with hypertrophic cardiomiopathy. Кapдиoвacкyляpнaя Тepaпия и Пpoфилaктикa 13(S2):3

    Google Scholar 

  • Bhagat S, Agarwal M, Roy V (2013) Serratiopeptidase: a systematic review of the existing evidence. Int J Surg 11(3):209–217

    Article  PubMed  Google Scholar 

  • Biswas S, Thakur V, Kaur P, Khan A, Kulshrestha S, Kumar P (2021) Blood clots in COVID-19 patients: simplifying the curious mystery. Med Hypotheses 146:110371

    Article  CAS  PubMed  Google Scholar 

  • Borth W (1992) α2 “Macroglobulin, a multifunctional binding protein with targeting characteristics. FASEB J 6(15):3345–3353

    Article  CAS  PubMed  Google Scholar 

  • Chandanwale A, Langade D, Sonawane D, Gavai P (2017) A randomized, clinical trial to evaluate efficacy and tolerability of trypsin: chymotrypsin as compared to serratiopeptidase and trypsin: bromelain: rutoside in wound management. Adv Ther 34:180–198

    Article  CAS  PubMed  Google Scholar 

  • Chander D, Khosla JK, Koul D, Hossain MM, Dar MJ, Chaubey A (2021) Purification and characterization of thermoactive serratiopeptidase from Serratia marcescens AD-W2. AMB Express 11:1–10

    Google Scholar 

  • Chandrasekaran SD, Vaithilingam M, Shanker R, Kumar S, Thiyur S, Babu V, Selvakumar JN, Prakash S (2015) Exploring the In vitro thrombolytic activity of nattokinase from a new strain Pseudomonas aeruginosa CMSS. Jundishapur J Microbiol 8(10):e23567. https://doi.org/10.5812/jjm.23567.PMID:26587211;PMCID:PMC4644271

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J et al (2018) Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9(6):7204

    Article  PubMed  Google Scholar 

  • Chopra D, Rehan H, Mehra P, Kakkar A (2009) A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction pain model. Int J Oral Maxillofac Surg 38(4):350–355

    Article  CAS  PubMed  Google Scholar 

  • Devi CS, Elizabeth Joseph R, Saravanan H, Naine SJ, Srinivansan VM (2013) Screening and molecular characterization of Serratia marcescens VITSD2: a strain producing optimum serratiopeptidase. Front Biol 8:632–639

    Article  CAS  Google Scholar 

  • Devlin H, Fulaz S, Hiebner DW, O’Gara JP, Casey E (2021). Enzyme-functionalized mesoporous silica nanoparticles to target Staphylococcus aureus and disperse biofilms. Int J Nanomed 16:1929–1942. https://doi.org/10.2147/IJN.S293190

    Article  Google Scholar 

  • Enerex. Serrapeptase Tablet. Retrieved from https://enerex.at/serrapeptase, Accessed 21 January 2023

  • Esch P, Gerngross H, Fabian A (1989) Reduction of postoperative swelling. Objective measurement of swelling of the upper ankle joint in treatment with serrapeptase–a prospective study. Fortschr Med 107(4):67–68

    CAS  PubMed  Google Scholar 

  • Ethiraj S, Gopinath S (2017) Production, purification, characterization, immobilization, and application of Serrapeptase: a review. Front Biol 12:333–348

    Article  CAS  Google Scholar 

  • Fadl N, Ahmed H, Booles H, Sayed A (2013) Serrapeptase and nattokinase intervention for relieving Alzheimer’s disease pathophysiology in rat model. Hum Exp Toxicol 32(7):721–735

    Article  CAS  PubMed  Google Scholar 

  • Garg R, Aslam S, Garg A, Walia R (2012) A prospective comparative study of serratiopeptidase and aceclofenac in upper and lower limb soft tissue trauma cases. Int J Pharmacol Pharm Technol 1(2):11–16

    Google Scholar 

  • Government of Canada HC. Natural Health Products Ingredients Database (2018) Serrapeptase. Retrieved from https://webprod.hc-sc.gc.ca/nhpid-bdipsn/atReq.do?atid=serrapeptase&lang=eng, Accessed 21 Jan 2023

  • Gupta KK, Rahman A, Kumar A, Gavel P, Asia P (2021) Adjuvant therapy with serratiopeptidase and Vitamin D for COVID-19 patients: a new perspective. Int J Med Sci 4:282–287

    Google Scholar 

  • Gupta V (2022) Serastar D Tablet. Retrieved from https://www.1mg.com/medicines/serastar-d-107554, Accessed 21 Jan 2023

  • Gupte V, Luthra U, Desai N (2017) Circular dichroism as a process analytical tool to monitor the quality of serratiopeptidase. Int J Eng Tech Sci Res 4(11):590–595

    Google Scholar 

  • Hamada K, Hata Y, Katsuya Y, Hiramatsu H, Fujiwara T, Katsube Y (1996) Crystal structure of serratia protease, a zinc-dependent proteinase from Serratia sp. E-15 containing a β-sheet coil motif at 2.0 AÅ resolution. J Biochemistry 119(5):844–851

    Article  CAS  Google Scholar 

  • Hamilos DL (2000) Chronic sinusitis. J Allergy Clin Immunol 106(2):213–227

    Article  CAS  PubMed  Google Scholar 

  • Hogan S, Zapotoczna M, Stevens N, Humphreys H, O’Gara J, O’Neill E (2017) Potential use of targeted enzymatic agents in the treatment of Staphylococcus aureus biofilm-related infections. J Hosp Infect 96(2):177–182

    Article  CAS  PubMed  Google Scholar 

  • Hosseinzadeh SA, Valizadeh V, Rouhani M, Mirkazemi S, Azizi M, Norouzian D, Ahangari Cohan R (2022) Novel serratiopeptidase exhibits different affinities to the substrates and inhibitors. Chem Biol Drug Des 100(4):553–563

    Article  CAS  PubMed  Google Scholar 

  • INDIA M (2022) Serratiopeptidase Brand name. Retrieved from http://www.medlineindia.com/musculoskeletal/serratiopeptidase.htm, Accessed 21 Jan 2023

  • Jadhav SB, Shah N, Rathi A, Rathi V, Rathi A (2020) Serratiopeptidase: Insights into the therapeutic applications. Biotechnology Reports 28:e00544

    Article  PubMed  PubMed Central  Google Scholar 

  • Jaiswal S, Mishra P (2018) Co-delivery of curcumin and serratiopeptidase in HeLa and MCF-7 cells through nanoparticles show improved anti-cancer activity. Mater Sci Eng 92:673–684

    Article  CAS  Google Scholar 

  • Jorissen E, Prox J, Bernreuther C, Weber S, Schwanbeck R, Serneels L, Snellinx A, Craessaerts K, Thathiah A, Tesseur I, Bartsch U, Weskamp G, Blobel CP, Glatzel M, De Strooper B, Saftig P (2010) The disintegrin/metalloproteinase ADAM10 is essential for the establishment of the brain cortex. J Neurosci 30(14):4833–4844. https://doi.org/10.1523/JNEUROSCI.5221-09.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalia VC, Patel SKS, Kang YC, Lee JK (2019) Quorum sensing inhibitors as antipathogens: biotechnological applications. Biotechnology advances 37(1):68–90. https://doi.org/10.1016/j.biotechadv.2018.11.006

    Article  CAS  PubMed  Google Scholar 

  • Kannan R, Kavitha R (2015) A comparative study of the anti-inflammatory properties of bromelain/serratiopeptidase as add on therapy to conventional treatment following impacted third molar surgery. World J Pharm Res 4:2595–2607

    CAS  Google Scholar 

  • Khanna A, Khanna M, Aggarwal A (2013) Serratia marcescens-a rare opportunistic nosocomial pathogen and measures to limit its spread in hospitalized patients. J Clin Diagn Res 7(2):243–246

    PubMed  Google Scholar 

  • Kumar S, Jana AK, Dhamija I, Maiti M (2014) Chitosan-assisted immobilization of serratiopeptidase on magnetic nanoparticles, characterization and its target delivery. J Drug Target 22(2):123–137

    Article  CAS  PubMed  Google Scholar 

  • Kumar M, Roy A, Rawat RS et al (2022) Identification and structural studies of natural inhibitors against SARS-CoV-2 viral RNA methyltransferase (NSP16). J Biomol Struct Dyn 40(24):13965–13975. https://doi.org/10.1080/07391102.2021.1997821

    Article  CAS  PubMed  Google Scholar 

  • Kumar M, Gaivin RJ, Khan S et al (2023) Definition of fatty acid transport protein-2 (FATP2) structure facilitates identification of small molecule inhibitors for the treatment of diabetic complications. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2023.125328

    Article  PubMed  PubMed Central  Google Scholar 

  • LaVoy EC, Fagundes CP, Dantzer R (2016) Exercise, inflammation, and fatigue in cancer survivors. Exerc Immunol Rev 22:82

    PubMed  PubMed Central  Google Scholar 

  • Leipner J, Saller R (2000) Systemic enzyme therapy in oncology: effect and mode of action. Drugs 59(4):769–780

    Article  CAS  PubMed  Google Scholar 

  • Li P, Kwok AH, Jiang J, Ran T, Xu D, Wang W, Leung FC (2015) Comparative genome analyses of Serratia marcescens FS14 reveals its high antagonistic potential. PLoS ONE 10(4):e0123061

    Article  PubMed  PubMed Central  Google Scholar 

  • Librate. Prodase Tablet. Retrieved from https://www.lybrate.com/medicine/prodase-10mg-tablet. Accessed 21 Jan 2023

  • Longhi C, Scoarughi GL, Poggiali F, Cellini A, Carpentieri A, Seganti L et al (2008) Protease treatment affects both invasion ability and biofilm formation in Listeria monocytogenes. Microb Pathog 45(1):45–52

    Article  CAS  PubMed  Google Scholar 

  • Ltd. MBP (2021) New dietry ingredient (NDI) safety information serratiopeptidase. Retrieved from https://downloads.regulations.gov/FDA-2021-S-0023-0078/content.pdf. Accessed 21 Jan 2023

  • Maeda H, Morihara K (1995) Serralysin and related bacterial proteinases. Methods in enzymology 248:395–413. https://doi.org/10.1016/0076-6879(95)48026-9

    Article  CAS  PubMed  Google Scholar 

  • Majima Y, Inagaki M, Hirata K, Takeuchi K, Morishita A, Sakakura Y (1988) The effect of an orally administered proteolytic enzyme on the elasticity and viscosity of nasal mucus. Arch Otorhinolaryngol 244:355–359

    Article  CAS  PubMed  Google Scholar 

  • Mali N, Wavikar P, Vavia P (2015) Serratiopeptidase loaded chitosan nanoparticles by polyelectrolyte complexation: in vitro and in vivo evaluation. AAPS PharmSciTech 16:59–66

    Article  CAS  PubMed  Google Scholar 

  • Mammdoh JK, Al-Mashhadanee FA, Al-Moula AD, Aljader GH (2020) Effect of topical serratiopeptidase on facial wound healing in rabbit. J Glob Pharma Technol 12(6):284–290

    CAS  Google Scholar 

  • Masuda S, Majima Y, Saida S, Sakakura Y (1989) Serratiopeptidase treatment of chronic sinusitis. 耳鼻咽喉科臨床 82(5):735–743. https://doi.org/10.5631/jibirin.82.735

    Article  Google Scholar 

  • Medibuddy. Amidase N Tablet. Retrieved from https://www.medibuddy.in/medicines/amidase-n-table. Accessed 21 Jan 2023

  • Medibuddy. Bidanzen Forte Tablet. Retrieved from https://www.medibuddy.in/medicines/bidanzen-forte-table. Accessed 21 Jan 2023 Medibuddy. Biosuganril Tm Tablet. Retrieved from https://www.medibuddy.in/medicines/biosuganril-tm-tablet. Accessed 21 Jan 2023

  • Medibuddy. Infla Tablet. Retrieved from https://www.medibuddy.in/medicines/infla-tablet. Accessed 21 Jan 2023

  • Medibuddy. Kineto Forte Tablet. Retrieved from https://www.medibuddy.in/medicines/kineto-forte-tablet. Accessed 21 Jan 2023

  • Medibuddy. Maxilase Tablet. Retrieved from https://www.medibuddy.in/medicines/maxilase-tablet. Accessed 21 Jan 2023

  • Medibuddy. Op Zed Tablet. Retrieved from https://www.medibuddy.in/medicines/op-zed-tablet. Accessed 21 Jan 2023

  • Medibuddy. Ratio D Tablet. Retrieved from https://www.medibuddy.in/medicines/ratio-d-tablet. Accessed 21 Jan 2023

  • Medibuddy. Serase Tablet. Retrieved from https://www.medibuddy.in/medicines/serase-tablet. Accessed 21 Jan 2023

  • Medibuddy. Seretochem Tablet. Retrieved from https://www.medibuddy.in/medicines/seretochem-tablet. Accessed 21 Jan 2023

  • Medibuddy. Super Heal Tablet. Retrieved from https://www.medibuddy.in/medicines/super-heal-tablet. Accessed 21 Jan 2023

  • Medibuddy. Amidase Tablet. Retrieved from https://www.medibuddy.in/medicines/amidase-tablet. Accessed 21 Jan 2023

  • Medibuddy. Seretochem D tablet. Retrieved from https://www.medibuddy.in/medicines/seretochem-d-tablet. Accessed 21 Jan 2023

  • Medindia. (2023). Serrapeptaseprice of 17 brands. Retrieved from https://www.medindia.net/drug-price/serrapeptase.htm. Accessed 21 Jan 2023

  • MedPlusmart. Serastar Plus Tablet. Retrieved from https://www.medplusmart.com/product/serastar-plus-tab_sera0177. Accessed 21 Jan 2023

  • Menon VD, Muthusekhar MR (2021) Effectiveness of anti-inflammatory properties of combination of bromelain, trypsin and rutoside with combination of diclofenac and serratiopeptidase following surgical removal of impacted mandibular third molar-a randomised double blinded clinical trial. Int J Dent Oral Sci 8(9):4217–4221. https://doi.org/10.19070/2377-8075-21000859

    Article  Google Scholar 

  • Metkar SK, Girigoswami A, Murugesan R, Girigoswami K (2017) In vitro and in vivo insulin amyloid degradation mediated by serratiopeptidase. Mater Sci Eng 70:728–735

    Article  CAS  Google Scholar 

  • Metkar SK, Girigoswami A, Vijayashree R, Girigoswami K (2020) Attenuation of subcutaneous insulin induced amyloid mass in vivo using lumbrokinase and serratiopeptidase. Int J Biol Macromolv 163:128–134

    Article  CAS  Google Scholar 

  • Metronic Biopharmaceuticals (2023) Serratiopeptidase Enteric Coated Granules. Retrieved from https://www.meteoricbiopharma.com/human/serratiopeptidaseenteric-coated-granules/. Accessed 21 Jan 2023

  • Misraulia K, Maheshwari P, Dongre J (2013) Studies on the efficacy of non-steroidal anti-inflammatory drugs and serratiopeptidase in dogs. Haryana Veterinarian 52:46–47

    Google Scholar 

  • Mohankumar A, Krishna Raj RH (2011) Production and characterization of serratiopeptidase enzyme from Serratia marcescens. Int J Biol 3(3):39–51

    Article  CAS  Google Scholar 

  • Mungantiwar A, Bhatt N, Shrivastava P, More J, Shaikh R (2021) A randomized, open-label, phase iv clinical study to compare the safety and efficacy of the fixed-dose combination of trypsin, bromelain, and rutoside versus serratiopeptidase in minor surgical wound. IJRAMT 2(6):308–313

    Google Scholar 

  • Nahar S, Mizan MFR, Ha AJ, Ha SD (2018) Advances and future prospects of enzyme-based biofilm prevention approaches in the food industry. Compr Rev Food Sci Food Saf 17(6):1484–1502

    Article  PubMed  Google Scholar 

  • Nair SR (2022) Serratiopeptidase: an integrated view of multifaceted therapeutic enzyme. Biomolecules 12(10):1468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakahama K, Yoshimura K, Marumoto R, Kikuchi M, Lee IS, Hase T, Matsubara H (1986) Cloning and sequencing of Serratia protease gene. Nucleic Acids Res 14(14):5843–5855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Narasimhan MK, Ethiraj S, Krishnamurthi T, Rajesh M (2018) Purification, biochemical, and thermal properties of fibrinolytic enzyme secreted by Bacillus cereus SRM-001. Prep Biochem Biotechnol 48(1):34–42. https://doi.org/10.1080/10826068.2017.1387560

    Article  CAS  PubMed  Google Scholar 

  • Pakhale SV, Bhagwat SS (2016) Purification of serratiopeptidase from Serratia marcescens NRRL B 23112 using ultrasound assisted three phase partitioning. Ultrason Sonochem 31:532–538

    Article  CAS  PubMed  Google Scholar 

  • Panagariya A, Sharma A (1999) A preliminary trial of serratiopeptidase in patients with carpal tunnel syndrome. J Assoc Physicians India 47(12):1170–1172

    CAS  PubMed  Google Scholar 

  • Pandya EJ, Kapupara P, Shah KV (2014) Development and validation of simultaneous estimation of diclofenac potassium, paracetamol and serratiopeptidase by first order derivative UV spectroscopy method in pharmaceutical formulation. J Chem Pharm Res 6(5):912–924

    Google Scholar 

  • Panthi VK, Jha SK, Chaubey R, Pangeni R (2021) Formulation and development of serratiopeptidase enteric coated tablets and analytical method validation by UV spectroscopy. Int J Anal Chem 2021:1–13

    Article  Google Scholar 

  • Papa R, Artini M, Cellini A, Tilotta M, Galano E, Pucci P et al (2013) A new anti-infective strategy to reduce the spreading of antibiotic resistance by the action on adhesion-mediated virulence factors in Staphylococcus aureus. Microb Pathog 63:44–53

    Article  CAS  PubMed  Google Scholar 

  • Passariello C, Lucchese A, Pera F, Gigola P (2012) Clinical, microbiological and inflammatory evidence of the efficacy of combination therapy including serratiopeptidase in the treatment of periimplantitis. Eur J Inflamm 10(3):463–472

    Article  CAS  Google Scholar 

  • Pharmacy, A. Flanzen Tablet. Retrieved from https://www.apollopharmacy.in/medicine/flanzen-5mg-tablet. Accessed 21 Jan 2023

  • PharmEasy. Seraim Tablet. Retrieved from https://pharmeasy.in/online-medicine-order/seraim-5mg-tab-77889. Accessed 21 Jan 2023

  • PharmEasy. Serra Tablet. Retrieved from https://pharmeasy.in/online-medicine-order/serra-10mg-tablet-15616. Accessed 21 Jan 2023

  • PharmEasy. Xondase Forte Tablet. Retrieved from https://pharmeasy.in/online-medicine-order/xondase-forte-tab-155649. Accessed 21 Jan 2023

  • PharmEasy. Dazen Tablet. Retrieved from https://pharmeasy.in/online-medicine-order/dazen-10mg-tab-42895. Accessed 21 Jan 2023

  • PharmEasy. Sheril Tablet. Retrieved from https://pharmeasy.in/online-medicine-order/sheril-10mg-tab-74134. Accessed 21 Jan 2023

  • Rajaram P, Bhattacharjee A, Ticku S (2016) Serratiopeptidase–A cause for spread of infection. J Clin Diagnostic Res 10 8 ZD31

  • Rani S, Singh N (2018) Formulation and characterization of periodontal films containing azithromycin and serratiopeptidase. Asian J Pharm Clin Res 11(5):205–209

    Article  Google Scholar 

  • Rath G, Johal E, Goyal AK (2011) Development of serratiopeptidase and metronidazole based alginate microspheres for wound healing. Artif Cells Nanomed Biotechnol 39(1):44–50

    CAS  Google Scholar 

  • Robinson PK (2015) Enzymes: principles and biotechnological applications. Essays Biochem 59:1

    Article  PubMed  PubMed Central  Google Scholar 

  • Rouhani M, Valizadeh V, Cohan RA, Norouzian D (2019) Computational design, structure refinement and molecular dynamics simulation of novel engineered serratiopeptidase analogs. J Biomol Struct Dyn 37(16):4171–4180

    Article  CAS  PubMed  Google Scholar 

  • Rouhani M, Valizadeh V, Molasalehi S, Norouzian D (2020) Production and expression optimization of heterologous serratiopeptidase. Iran J Public Health 49(5):931

    PubMed  PubMed Central  Google Scholar 

  • Rouhani M, Valizadeh V, Aghai A, Pourasghar S, Molasalehi S, Cohan R, Norouzian D (2022) Design, expression and functional assessment of novel engineered serratiopeptidase analogs with enhanced protease activity and thermal stability. World J Microbiol Biotechnol 38(1):17

    Article  CAS  Google Scholar 

  • Rouhani M, Valizadeh V, Bakhshandeh H, Hosseinzadeh SA, Molasalehi S, Atyabi SM, Norouzian D (2023) Improved anti-biofilm activity and long-lasting effects of novel serratiopeptidase immobilized on cellulose nanofibers. Appl Microbiol Biotechnol 107(21):6487–6496. https://doi.org/10.1007/s00253-023-12734-7

    Article  CAS  PubMed  Google Scholar 

  • Selan L, Berlutti F, Passariello C, Comodi-Ballanti M, Thaller M (1993) Proteolytic enzymes: a new treatment strategy for prosthetic infections? Antimicrob Agents Chemother 37(12):2618–2621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selan L, Papa R, Ermocida A, Cellini A, Ettorre E, Vrenna G et al (2017) Serratiopeptidase reduces the invasion of osteoblasts by Staphylococcus aureus. Int J Immunopathol Pharmacol 30(4):423–428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selan L, Artini M, Papa R (2016) Compounds from natural sources for new diagnostics and drugs against biofilm infections. In: Microbial biofilms. importance and applications. InTech, London, pp 487–509

  • Shahbaz M, Kamran SH, Anwar R (2021) Amelioration of bleomycin and methotrexate-induced pulmonary toxicity by serratiopeptidase and fisetin. Nutr Cancer 73(11–12):2774–2784

    Article  CAS  PubMed  Google Scholar 

  • Sharma C, Jha NK, Meeran MN, Patil CR, Goyal SN, Ojha S (2021) Serratiopeptidase, a serine protease anti-inflammatory, fibrinolytic, and mucolytic drug, can be a useful adjuvant for management in COVID-19. Front Pharmacol 12:603997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shende PK, Bakal RL, Gaud R, Batheja KN, Kawadiwale MS (2015) Modulation of serratiopeptidase transdermal patch by lipid-based transfersomes. J Adhes Sci Technol 29(23):2622–2633

    Article  CAS  Google Scholar 

  • Shende P, Gaud R, Bakal R, Yeole Y (2016) Clove oil emulsified buccal patch of serratiopeptidase for controlled release in toothache. J Bioequiv Availab 8(3):134–139

    Google Scholar 

  • Shi J, Kantoff PW, Wooster R, Farokhzad OC (2017) Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 17(1):20–37

    Article  CAS  PubMed  Google Scholar 

  • Shinde UA, Kanojiya SS (2014) Serratiopeptidase niosomal gel with potential in topical delivery. J Pharm 2014:382959. https://doi.org/10.1155/2014/382959

    Article  Google Scholar 

  • Singh KP, Chhabra G, Sharma V, Pathak K (2014) Thermosensitive periodontal sol of ciprofloxacin hydrochloride and serratiopeptidase: pharmaceutical and mechanical analysis. Int J Pharm Investig 4(1):5

    Article  PubMed  PubMed Central  Google Scholar 

  • Singh R, Kumar M, Mittal A, Mehta PK (2016) Microbial enzymes: industrial progress in 21st century. 3 Biotech 6:1–15

    Article  PubMed  Google Scholar 

  • Sivaramakrishnan G, Sridharan K (2018) Role of serratiopeptidase after surgical removal of impacted molar: a systematic review and meta-analysis. J Maxillofac Surg 17:122–128

    Google Scholar 

  • Srinivasan V, Ak S, Mondal M, Dhar SC (2013) Screening for staphylokinase producing staphylococcus spp. from bovine milk sample. Int J Pharm Pharm Sci 5(2):601–604

    Google Scholar 

  • Srivastava V (2019) Investigating biotechnological and mechanistic aspects of repeat in-toxin family metalloprotease-serratiopeptidase. IIT Delhi

    Google Scholar 

  • Srivastava S, Singh D, Patel S, Singh MR (2017) Treatment of rheumatoid arthritis by targeting macrophages through folic acid tailored superoxide dismutase and serratiopeptidase. J Drug Deliv Sci Technol 41:431–435

    Article  CAS  Google Scholar 

  • Srivastava V, Mishra S, Chaudhuri TK (2019) Enhanced production of recombinant serratiopeptidase in Escherichia coli and its characterization as a potential biosimilar to native biotherapeutic counterpart. Microb Cell Factor 18(1):1–15

    Article  Google Scholar 

  • Steiger S, Harper JL (2013) Mechanisms of spontaneous resolution of acute gouty inflammation. Curr Rheumatol Rep 16:392. https://doi.org/10.1007/s11926-013-0392-5

    Article  CAS  Google Scholar 

  • Subathradevi C, Saha A, Mondal M, Dhar S, Suganthi V, Selvarajan E, Mohanasrinivasan V (2013) Screening for staphylokinase producing Staphylococcus SPP. from bovine milk sample. Int J Pharm Pharm Sci 5(2):601–604

    Google Scholar 

  • Sugathan S, Pradeep NS, Abdulhameed S (2017) In Shiburaj Sugathan, N. S. Pradeep, Sabu Abdulhameed Bioresources and bioprocess in biotechnology: volume 2 exploring potential biomolecules. Springer Singapore. Singapore

  • Suresh KV, Patil MR, Desai R, Tauro DP, KNS SB, Parkar MI, Babaji HV, (2015) Comparison of clinical efficacy of methylprednisolone and serratiopeptidase for reduction of postoperative sequelae after lower third molar surgery. J Clin Exp Dent 7(2):e197

    PubMed  PubMed Central  Google Scholar 

  • Tandon S, Sharma A, Singh S, Sharma S, Sarma SJ (2021) Therapeutic enzymes: discoveries, production and applications. J Drug Deliv Sci Technol 63:102455

    Article  CAS  Google Scholar 

  • Taneja K, Bajaj BK, Kumar S, Dilbaghi N (2017) Production, purification and characterization of fibrinolytic enzyme from Serratia sp. KG-2-1 using optimized media. 3 Biotech 7:1–15

    Article  CAS  Google Scholar 

  • U.S.Food and Drug Administration (1996) NDI 4 - Enzyme-Peptidase (Trade Name: serratiopeptidase from Specialty Enzymes and Biochemicals Co. Retrieved from https://www.regulations.gov/document/FDA-1996-S-0502-0014. Accessed 21 Jan 2023

  • Vellard M (2003) The enzyme as drug: application of enzymes as pharmaceuticals. Curr Opin Biotechnol 14(4):444–450

    Article  CAS  PubMed  Google Scholar 

  • Verma V (2020) Different analytical procedures for the estimation of serratiopeptidase. Int Pharm Sci 11:1. https://doi.org/10.31531/2231-5896.1000107

    Article  Google Scholar 

  • Vijayan V, Kumar KJ, Muralidharan S, Parasuraman S (2015) Formulation and characterization of novel ethanolic carrier for improves penetration of serratiopeptidase. Res Rev J Drug Formul Dev Prod 2(1):1–6

    Google Scholar 

  • Vitalshop. Serrapeptidase 240,000 EU* plus Cat’s Claw extract. Retrieved from https://drreinwald.com/shop/serrazym-plus/. Accessed 21 Jan 2023

  • Vitazan. (2023). Serratiopeptidase 120,000 SU. Retrieved from https://vitazan.com/product/serratiopeptidase-120000/. Accessed 21 Jan 2023

  • Wu D, Ran T, Wang W, Xu D (2016) Structure of a thermostable serralysin from Serratia sp FS14 at 1.1 Å resolution. Acta Crystallogr Sec F Struct Biol Commun 72(1):10–15

    Article  CAS  Google Scholar 

  • Ząbczyk M, Natorska J, Undas A (2021) Fibrin clot properties in atherosclerotic vascular disease: from pathophysiology to clinical outcomes. J Clin Med 10(13):2999

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Morrison AJ, Thibodeau PH (2015) Interdomain contacts and the stability of serralysin protease from Serratia marcescens. PLoS ONE 10(9):e0138419

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Conway JF, Thibodeau PH (2012) Calcium-induced Folding and Stabilization of the Pseudomonas aeruginosa Alkaline Protease. The Journal of biological chemistry 287:4311–4322. https://doi.org/10.1074/jbc.M111.310300

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors wish to express their deep gratitude to all who provided support during the course of this research. This project was financially supported by Pasteur Institute of Iran.

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Authors and Affiliations

  1. New Technologies Research Group, Nanobiotechnology Department, Pasteur Institute of Iran, Tehran, Iran

    Seyedeh Bahareh Hosseini & Vahideh Valizadeh

  2. Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

    Masoumeh Azizi

  3. Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran

    Seyed Ali Nojoumi

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  1. Seyedeh Bahareh Hosseini
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  2. Masoumeh Azizi
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  3. Seyed Ali Nojoumi
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  4. Vahideh Valizadeh
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Contributions

SBH contributed by collecting and analyzing the data and drafted the paper. MA and SAN critically revised the manuscript. VV designed the work, supervised the study and critically revised the manuscript.

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Correspondence to Vahideh Valizadeh.

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Hosseini, S.B., Azizi, M., Nojoumi, S.A. et al. An up-to-date review of biomedical applications of serratiopeptidase and its biobetter derivatives as a multi-potential metalloprotease. Arch Microbiol 206, 180 (2024). https://doi.org/10.1007/s00203-024-03889-6

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