Abstract
Proteins are very important for the smooth functioning of the human body since they act as structural components, enzymes, signaling molecules and cell-cell interaction mediator. Mutations in genes, might result in improper expression or maturation of proteins leading to mild or serious abnormalities. In many cases, external supply of such functionally active proteins in the body subsidizes protein related abnormalities. Some protein related abnormalities such as diabetes are common in a large section of public where insulin is the best source of protein to streamline the proper body functions. However, large productions of such proteins are required for the treatment of deficient patients. In such a scenario, natural sources are not sufficient enough to match the required demand and chemical synthesis increases the cost. However, recombinant DNA (r-DNA) technology using a host expressing system fulfilled the large-scale therapeutics requirement at a low cost. Bacterial systems when compared to other organisms are the most studied and easy to handle in generating these proteins. Apart from recombinant therapeutic protein production, bacteria naturally produce peptide antibiotics as defense metabolites which can be used to treat bacterial infections. Peptide antibiotics are thus very useful products. However, are naturally produced in minute concentrations in bacterial systems. Hence r-DNA technology is generally preferred for mass production. In this chapter review, we have discussed the major therapeutic proteins, peptide antibiotics and their industrial scale production. We also elaborated the benefits of a bacterial host system for a large-scale production of these recombinant products.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Afonin S, Dürr UHN, Wadhwani P et al (2008) Solid state NMR structure analysis of the antimicrobial peptide gramicidin-S in lipid membranes: and self-assembly as a β-barrel. Anion Sens:139–154. https://doi.org/10.1007/128
Ahmed H (2004) Principles and reactions of protein extraction, purification, and characterization. Princ React Protein Extr Purification, Charact, pp 1–389
Asenjo JA, Herrera L, Byrne B (1989) Development of an expert system for selection and synthesis of protein purification processes. J Biotechnol 11:275–298. https://doi.org/10.1016/0168-1656(89)90123-5
Awais M, Pervez A, Qayyum S, Saleem M (2008) Effects of glucose, incubation period and pH on the production of peptide antibiotics by Bacillus pumilus. Afr J Microbiol Res 2:114–119
Barfoed HC (1987) Insulin production technology. Chem Eng Prog 83(10):49–54
Benedict RG, Langlykke AF (1947) Antibiotic activity of Bacillus polymyxa. J Bacteriol 54(1):24
Beverley B, Eschwège E (2003) The diagnosis and classification of diabetes and impaired glucose tolerance. Textbook of diabetes (1 edn.) John C Pickup and Gareth Williams Third edition: 2.1
Brink AJ, Richards GA, Colombo G, Bortolotti F, Colombo P, Jehl F (2014) Multi component antibiotic substances produced by fermentation: implications for regulatory authorities, critically ill patients and generics. Int J Antimicrob Agents 43:1–6
Chance R, Glazer N, Wishner K (1999) Insulin Lispro (Humalog) in biopharmaceuticals, an industrial perspective. Dordrecht, pp 149–172
Chien-Hung C, Yi-Chun C, Sheng-Nan L, Chuan-Mo L, Tsung-Hui H, Chao-Hung H (2014) Serum hepatitis surface antigen level predict treatment response to nucleos(t)ide analogues. World J Gastroenterol 20(24):7686–7695
Chisti Y, Moo-young M (1986) Disruption of microbial cells for intracellular products. Butterworth, pp 1–11
Costa S, Almeida A, Castro A, Domingues L (2014) Fusion tags for protein solubility, purification, and immunogenicity in Escherichia coli: the novel Fh8 system. Front Microbiol 5. https://doi.org/10.3389/fmicb.2014.00063
Cregg JM, Barringer KJ, Hessler AY, Madden KR (1985) Pichia pastoris as a host system for transformations. Mol Cell Biol 5:3376–3385. https://doi.org/10.1128/mcb.5.12.3376
De Hoff PL, Brill LM, Hirsch AM (2009) Plant lectins: the ties that bind in root symbiosis and plant defense. Mol Genet Genomics 282:1–15. https://doi.org/10.1007/s00438-009-0460-8
Demain AL, Aharonowitz Y, Martin JF (1983) Metabolite control of secondary biosynthetic pathways. Addison-Wesley, pp 49–67
Dhillon S (2018) Eculizumab: a review in generalized myasthenia gravis. Drugs 78:367–376. https://doi.org/10.1007/s40265-018-0875-9
Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and the progression of long term complications in insulin-dependent diabetes mellitus. J Med 329:977–978
Dias R, Machado S, Migliolo L, Franco L (2015) Insights into animal and plant lectins with antimicrobial activities. Molecules 20:519–541
Dixon RA, Chopra I (1986) Leakage of periplasmic proteins from Escherichia coli mediated by polymyxin B nonapeptide. Antimicrob Agents Chemother 29:781–788. https://doi.org/10.1128/AAC.29.5.781
Doulah MS (1977) Mechanism of disintegration of biological cells in ultrasonic cavitation. Biotechnol Bioeng 19:649–660. https://doi.org/10.1002/bit.260190504
Falagas ME, Rafailidis PI, Matthaiou DK (2010) Resistance to polymyxins: mechanisms, frequency and treatment options. Drug Resist Updat 13:132–138. https://doi.org/10.1016/j.drup.2010.05.002
Figueroa B, Ailor E, Osborne D, Hardwick JM, Reff M, Betenbaugh MJ (2007) Enhanced cell culture performance using inducible anti-apoptotic genes E1B–19 K and in the production of a monoclonal antibody with Chinese hamster ovary cells. Biotechnol Bioeng 97:877–892
Gallardo-Godoy A, Muldoon C, Becker B et al (2016) Activity and predicted nephrotoxicity of synthetic antibiotics based on Polymyxin B. J Med Chem 59:1068–1077. https://doi.org/10.1021/acs.jmedchem.5b01593
Gasteiger E, Gattiker A, Hoogland C et al (2003) ExPASy: the proteomics server for in-depth protein knowledge and analysis. Nucl Acids Res 31:3784–3788. https://doi.org/10.1093/nar/gkg563
Gemeiner P, Mislovičová D, Tkáč J et al (2009) Lectinomics. II. A highway to biomedical/clinical diagnostics. Biotechnol Adv 27:1–15. https://doi.org/10.1016/j.biotechadv.2008.07.003
Gomes A, Carmo T, Carvalho L, Bahia F, Parachin N (2018) Comparison of yeasts as a host for recombinant protein production. Microorganisms 6(2):38
Gottesman S (1996) Proteases and their targets in Escherichia coli. Annu Rev Genet 30:465–506. https://doi.org/10.1146/annurev.genet.30.1.465
Graumann K, Premstaller A (2006) Manufacturing of recombinant therapeutic proteins in microbial systems. Biotechnol J 1:164–186
Grodberg J, Dunn JJ (1988) ompT encodes the Escherichia coli outer membrane protease that cleaves T7 RNA polymerase during purification. J Bacteriol 170:1245–1253. https://doi.org/10.1128/jb.170.3.1245-1253.1988
Hammon J, Palanivelu DV, Chen J et al (2009) A green fluorescent protein screen for identification of well-expressed membrane proteins from a cohort of extremophilic organisms. Protein Sci 18:121–133. https://doi.org/10.1002/pro.18
Hancock RE (1997) Peptide antibiotics. Lancet 349:418–422
Hannig G, Makrides S (1998) Strategies for optimizing heterologous protein expression in Escherichia Coli. Tibtech:54–61
Harrison RL, Jarvis DL (2006) Protein N-glycosylation in the Baculovirus-insect cell expression system and engineering of insect cells to produce “Mammalianized” recombinant glycoproteins. Adv Virus Res 68:159–191. https://doi.org/10.1016/S0065-3527(06)68005-6
Heinemann L, Starke AAR, Hohmann A, Berger M (1992) Timing between the subcutaneous administration of insulin and consumption of a carbohydrate rich meal. Horm Metab Res Suppl:137–139
Hillson DA, Lambert N, Freedman RB (1984) Formation and isomerization of disulfide bonds in proteins: protein disulfide-isomerase. Methods Enzymol 107:281–294. https://doi.org/10.1016/0076-6879(84)07018-X
Hirabayashi J, Sakakura Y, Kasai K (1993) Production of intact recombinant proteins in Escherichia Coli. Lectins Glycobiol:474–481
Huang CJ, Lin H, Yang X (2012) Industrial production of recombinant therapeutics in Escherichia coli and its recent advancements. J Ind Microbiol Biotechnol 39:383–399. https://doi.org/10.1007/s10295-011-1082-9
Husain Q (2010) β galactosidases and their potential applications: a review. Crit Rev Biotechnol 30:41–62. https://doi.org/10.3109/07388550903330497
Jenkins N (2007) Modifications of therapeutic proteins: challenges and prospects. Cytotechnology 53:121–125. https://doi.org/10.1007/s10616-007-9075-2
Jenkins N, Parekh RB, James DC (1996) Getting the glycosylation right: implications for the biotechnology industry. Nat Biotechnol 14:975–981. https://doi.org/10.1038/nbt0896-975
Joseph J, Jaison V, Jain K, Kakkar N, Jacob J (2012) Erythropoietin use and abuse. Indian J Endocrinol Metabol 16(2):220–227
Kenig M, Peternel Š, Gaberc-Porekar V, Menart V (2006) Influence of the protein oligomericity on final yield after affinity tag removal in purification of recombinant proteins. J Chromatogr A 1101:293–306. https://doi.org/10.1016/j.chroma.2005.09.089
Kimple ME, Brill AL, Pasker RL (2013) Overview of affinity tags for protein purification. Curr Protoc Protein Sci:1–23. https://doi.org/10.1002/0471140864.ps0909s73
Kleinkauf H, von Dohren H (1988) Peptide antibiotics, f3-lactams, and related compounds. 8
Koivu J, Myllylä R, Helaakoski T et al (1987) A single polypeptide acts both as the beta subunit of prolyl 4-hydroxylase and as a protein disulfide-isomerase. J Biol Chem 262:6447–6449
Lam SK, Ng TB (2011) Lectins: production and practical applications. Appl Microbiol Biotechnol 89:45–55. https://doi.org/10.1007/s00253-010-2892-9
Lannoo N, Vervecken W, Proost P et al (2007) Expression of the nucleocytoplasmic tobacco lectin in the yeast Pichia pastoris. Protein Expr Purif 53:275–282. https://doi.org/10.1016/j.pep.2007.01.007
Li J, Nation RL, Turnidge JD et al (2006) Colistin: the re-emerging antibiotic for multidrug-resistant gram-negative bacterial infections. Lancet Infect Dis 6:589–601. https://doi.org/10.1016/S1473-3099(06)70580-1
Lu P, Takai K, Weaver VM, Werb Z (2011) Extracellular matrix degradation and remodelling in development and disease. Cold Spring Harb Perspect Biol 3:12
Luo S, Zhangsun D, Tang K (2005) Functional GNA expressed in Escherichia coli with high efficiency and its effect on Ceratovacuna lanigera zehntner. Appl Microbiol Biotechnol 69:184–191. https://doi.org/10.1007/s00253-005-0042-6
Mastick CC, Brady MJ, Printen JA et al (1998) Spatial determinants of specificity in insulin action. Mol Cell Biochem 182:65–71. https://doi.org/10.1023/A:1006835430797
Metcalf D (2008) Hematopoietic cytokines. Blood 111:485–491
Middelberg APJ (2000) 2 Microbial cell disruption by high-pressure homogenization. 11–21. https://doi.org/10.1007/978-1-59259-027-8_2
Mitchell AC, Briquez PS, Hubbell JA, Cochran JR (2016) Engineering growth factors for regenerative medicine applications. Acta Biomater 30:1–12. https://doi.org/10.1016/j.actbio.2015.11.007
Morello E, Bermúdez-Humarán LG, Llull D et al (2007) Lactococcus lactis, an efficient cell factory for recombinant protein production and secretion. J Mol Microbiol Biotechnol 14:48–58. https://doi.org/10.1159/000106082
Nagesh T, Srivastava A (2019) Recent developments in bioprocessing of recombinant proteins: expression hosts and process development. Front Bioeng Biotecnol 7:420
Nakano MM, Zuber P (1990) Molecular biology of antibiotic production in Bacillus. Crit Rev Biotechnol 10:223–240
Nation RL, Li J, Cars O et al (2014) Consistent global approach on reporting of colistin doses to promote safe and effective use. Clin Infect Dis 58:139–141. https://doi.org/10.1093/cid/cit680
Nilsson J, Jonasson P, Samuelsson E et al (1996) Integrated production of human insulin and its C-peptide. J Biotechnol 48:241–250. https://doi.org/10.1016/0168-1656(96)01514-3
Oliveira C, Costa S, Teixeira JA, Domingues L (2009) cDNA cloningand functional expression of the alphaD-galactose-binding lectinfrutalin in Escherichia coli. Mol Biotechnol 43:212–220
Oliveira C, Teixeira JA, Domingues L (2013) Recombinant lectins: an array of tailor-made glycan-interaction biosynthetic tools. Crit Rev Biotechnol 33:66–80. https://doi.org/10.3109/07388551.2012.670614
Omura S, Ikeda H, Ishikawa J et al (2001) Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites. Proc Natl Acad Sci U S A 98:12215–12220. https://doi.org/10.1073/pnas.211433198
Ostrovski DN, Eremin VA, Udalova TP, Kharatian EF (1988) The cell wall of Bacillus brevis producing gramicidin S, a cyclodecapeptide antibiotic. Mikrobiologiia 57:1017–1023
Panesar PS, Panesar R, Singh RS et al (2006) Microbial production, immobilization and applications of β-D-galactosidase. J Chem Technol Biotechnol 81:530–543. https://doi.org/10.1002/jctb.1453
Peternel S (2013) Bacterial cell disruption: a crucial step in protein production. New Biotechnol 30:250–254. https://doi.org/10.1016/j.nbt.2011.09.005
Peternel S, Komel R (2010) Isolation of biologically active nanomaterial (inclusion bodies) from bacterial cells. Microb Cell Factories 9:1–16. https://doi.org/10.1186/1475-2859-9-66
Porekar V, Menart V (2001) Perpectives of immobilized metal affinity chromatography. Eur J Biochem 49:335–360
Procopio R, Da Silva I, Martins M, Azevedo J, Araujo J (2012) Antibiotics produced by streptomyces. Br J Infect Dis 16(5):466–471
Procopio T, Moura M, Albuquerque L, Gomes F, Santos N, Coelho L, Pontual E, Paiva P, Napoleao T (2017) Antibacterial lectins: action mechanisms, defensive roles and biotechnological roles. Antibacterials: Chapter 3 Nova Science Publishers, pp 70–90
Puetz J, Wurm FM (2019) Recombinant proteins for industrial versus pharmaceutical purposes: a review of process and pricing. PRO 7:476. https://doi.org/10.3390/pr7080476
Raemaekers RJM, De Muro L, Gatehouse JA, Fordham-Skelton AP (1999) Functional phytohemagglutinin (PHA) and Galanthus nivalis agglutinin (GNA) expressed in Pichia pastoris. Correct N-terminal processing and secretion of heterologous proteins expressed using the PHA-E signal peptide. Eur J Biochem 265:394–403. https://doi.org/10.1046/j.1432-1327.1999.00749.x
Rao P, Kroon D (1993) Orthoclone OKT3. Stability and characterization of protein and peptide drugs, pp 135–158
Rodríguez-Carmona E, Cano-Garrido O, Seras-Franzoso J et al (2010) Isolation of cell-free bacterial inclusion bodies. Microb Cell Factories 9:1–9. https://doi.org/10.1186/1475-2859-9-71
Santagastino E (2014) A new recombinant factor VIII: from genetics to clinical use. Drug Des Devel Ther 8:2507–2515
Seeger RC (2011) Immunology and immunotherapy of neuro blastoma. Semin Cancer Biol 21:229–237
Sen KS, Haque FS, Pal CS (1995) Nutrient optimization for production of broad-spectrum antibiotics by Streptomyces antibioticus. Microbial Hung 42:155–162
Snell N, Ijichi K, Lewis JC (1955) Paper chromatographic identification of polypeptide gram positive inhibiting antibiotics. Western Utilization Research Branch
Strausberg RL, National Institutes of Health Bethesda M, Strausberg, Susan L, University of Maryland, Rockville M (2000) Overview of protein expression in Saccharomyces cerevisiae. Curr Protoc Protein Sci:1–7
Streicher H, Sharon N (2003) Recombinant plant lectins and their mutants. Methods Enzymol 363:47–77. https://doi.org/10.1016/S0076-6879(03)01043-7
Stubbs ME, Carver JP, Dunn RJ (1986) Production of pea lectin in Escherichia coli. J Biol Chem 261:6141–6144
Takagi H, Kadowaki K, Udaka S (1989) Screening and characterization of protein-hyperproducing bacteria without detectable exoprotease activity. Agric Biol Chem 53:691–699. https://doi.org/10.1080/00021369.1989.10869382
Tateno H, Winter H, Goldstein I (2004) Escherichia coli and characterization of the recombinant Neu5Acalpha2, 6Galbeta1, 4GlcNAc-specific high-affinity lectin and its mutants from the mushroom Polyporus. Biochem J 382:667–675
Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK (2016) Extracellular matrix structure. Adv Drug Deliv Rev 97:4–27. https://doi.org/10.1016/j.addr.2015.11.001
Upadhyay SK, Saurabh S, Rai P et al (2010) SUMO fusion facilitates expression and purification of garlic leaf lectin but modifies some of its properties. J Biotechnol 146:1–8. https://doi.org/10.1016/j.jbiotec.2010.01.013
Vajo Z, Fawcett J, Hamel FG, Bennett RG, Duckworth WC (2001) Insulin and analogue effects on protein degradation in different cell types. J Biol Chem 276(15):11552–11558
Vallejo LF, Rinas U (2004) Strategies for the recovery of active proteins through refolding of bacterial inclusion body proteins. Microb Cell Factories 3:11
Wacker M, Linton D, Hitchen PG et al (2002) Glycosylation Campylobacter jejuni N-linked. Science (80-):2649
Waksman SA (1940) Microbes in a changing world. Sci Monthly 51:422–427
Waksman A (1970) Success and failures in the search of antibiotics. Institute of Microbiology, pp 1–16
Walsh G, Jefferis R (2006) Post-translational modifications in the context of therapeutic proteins. Nat Biotechnol 24:1241–1252. https://doi.org/10.1038/nbt1252
Wang F, Qin L, Pace CJ et al (2012) Solubilized gramicidin a as potential systemic antibiotics. Chembiochem 13:51–55. https://doi.org/10.1002/cbic.201100671
Watanabe K (2004) Collagenolytic proteases from bacteria. Appl Microbiol Biotechnol 63:520–526. https://doi.org/10.1007/s00253-003-1442-0
Watve MG, Tickoo R, Jog MM, Bhole BD (2001) How many antibiotics are produced by the genus Streptomyces? Arch Microbiol 176:386–390. https://doi.org/10.1007/s002030100345
Wurm FM (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22:1393–1398. https://doi.org/10.1038/nbt1026
Yeh CM, Kao BY, Peng HJ (2009) Production of a recombinant type 1 antifreeze protein analogue by L. lactis and its applications on frozen meat and frozen dough. J Agric Food Chem 57:6216–6223. https://doi.org/10.1021/jf900924f
Yousaf M (1997) Studies on the cultural conditions for the production of antibiotic bacitracin by B. licheniformis. Islamia University Bahawalpur Pakistan, pp 1–15
Zhao X, Li G, Liang S (2013) Several affinity tags commonly used in chromatographic purification. J Anal Methods Chem 2013. https://doi.org/10.1155/2013/581093
Acknowledgement
We thank the Department of Biotechnology, Ministry of Science and Technology, India, for the BioCare women scientist fellowship and Goa University for providing research facilities.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Kerkar, K., Tiwari, M., Tiwari, D.K., Kerkar, S. (2021). Industrial Scale Production of Important Therapeutic Proteins Using Bacterial Expression System. In: Arora, P.K. (eds) Microbial Products for Health, Environment and Agriculture . Microorganisms for Sustainability, vol 31. Springer, Singapore. https://doi.org/10.1007/978-981-16-1947-2_8
Download citation
DOI: https://doi.org/10.1007/978-981-16-1947-2_8
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-16-1946-5
Online ISBN: 978-981-16-1947-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)