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Scale-Up of Engineering Strain for Industrial Applications

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Microbial Engineering for Therapeutics

Abstract

The scale-up of industrial processes are required to maintain optimum and homogenous condition for reaction so that it will eventually lead to increase in product yield and quality that is the fundamental issue for industrial fermentation processes. For each individual product, process and facility, suitable strategies have to be elaborated by a comprehensive and detailed process characterization, identification of the most relevant process parameters influencing product yield and quality and their establishment as scale-up parameters to be kept constant as far as possible. Physical variables, which can only be restrictedly kept constantans single parameters, may be combined with other pertinent parameters to appropriate mathematical groups or dimensionless terms. Appropriately applicable strategies have to be developed that will increase metabolic accuracy and will minimize exposure of the strain to stress. Mutagenesis is the common method to obtain microbial strain producing industrially important metabolites. However, identification of the genes responsible to control the production of the metabolites is one of the key factors. Research related to investigation of the genetics and physiology of a microorganism eventually leads to obtain the knowledge which can then be used for strain development processes. To maximize the potential and efficiency of the developed strain the fermentation process parameter should be continuously optimized. In the chapter, the method to develop the potential microbial strains and the strategies employed for optimization of the fermentation processes are discussed and analyzed.

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References

  • Ansorge MB, Kula MR (2000) Production of recombinant L-leucine dehydrogenase from Bacillus cereus in pilot scale using the runaway replication system E. coli [piet98]. Biotechnol Bioeng 68(5):557–562

    Article  CAS  PubMed  Google Scholar 

  • Behera HT et al (2020) Production of N-acetyl chitooligosaccharide by novel Streptomyces chilikensis strain RC1830 and its evaluation for anti-radical, anti-inflammatory, anti-proliferative and cell migration potential. Bioresour Technol Rep 11:100428

    Article  Google Scholar 

  • Boehl D et al (2003) Chemometric modelling with two-dimensional fluorescence data for Claviceps purpurea bioprocess characterization. J Biotechnol 105(1–2):179–188

    Article  CAS  PubMed  Google Scholar 

  • Buchholz A, Takors R, Wandrey C (2001) Quantification of intracellular metabolites in Escherichia coli K12 using liquid chromatographic-electrospray ionization tandem mass spectrometric techniques. Anal Biochem 295(2):129–137

    Article  CAS  PubMed  Google Scholar 

  • Bylund F et al (2000) Influence of scale-up on the quality of recombinant human growth hormone. Biotechnol Bioeng 69(2):119–128

    Article  CAS  PubMed  Google Scholar 

  • Castan A, Enfors SO (2002) Formate accumulation due to DNA release in aerobic cultivations of Escherichia coli. Biotechnol Bioeng 77(3):324–328

    Article  CAS  PubMed  Google Scholar 

  • Collins GE et al (2004) Compact, high voltage power supply for the lab-on-a-chip. Lab Chip 4(4):408–411

    Article  CAS  PubMed  Google Scholar 

  • Crater JS, Lievense JC (2018) Scale-up of industrial microbial processes. FEMS Microbiol Lett 365(13):fny138

    Article  CAS  PubMed Central  Google Scholar 

  • d’Anjou MC, Daugulis AJ (2000) Mixed-feed exponential feeding for fed-batch culture of recombinant methylotrophic yeast. Biotechnol Lett 22(5):341–346

    Article  Google Scholar 

  • Dickinson TA et al (1998) Current trends ‘inartificial-nose’ technology. Trends Biotechnol 16(6):250–258

    Article  CAS  PubMed  Google Scholar 

  • Enfors S-O et al (2001) Physiological responses to mixing in large scale bioreactors. J Biotechnol 85(2):175–185

    Article  CAS  PubMed  Google Scholar 

  • Fenton D et al (1997) Control of norleucine incorporation into recombinant proteins. Google Patents

    Google Scholar 

  • Futcher A, Cox B (1984) Copy number and the stability of 2-micron circle-based artificial plasmids of Saccharomyces cerevisiae. J Bacteriol 157(1):283–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gabig-Ciminska M et al (2004) Electric chips for rapid detection and quantification of nucleic acids. Biosens Bioelectron 19(6):537–546

    Article  CAS  PubMed  Google Scholar 

  • Hall JW et al (1996) Near-infrared spectroscopic determination of acetate, ammonium, biomass, and glycerol in an industrial Escherichia coli fermentation. Appl Spectrosc 50(1):102–108

    Article  CAS  Google Scholar 

  • Käppeli O (1987) Regulation of carbon metabolism in Saccharomyces cerevisiae and related yeasts. In: Advances in microbial physiology. Elsevier, Burlington, pp 181–209

    Google Scholar 

  • Kiick K, Weberskirch R, Tirrell D (2001) Identification of an expanded set of translationally active methionine analogues in Escherichia coli. FEBS Lett 502(1–2):25–30

    Article  CAS  PubMed  Google Scholar 

  • Ko YS, Kim JW, Lee JA, Han T, Kim GB, Park JE, Lee SY (2020) Tools and strategies of systems metabolic engineering for the development of microbial cell factories for chemical production. Chem Soc Rev 49(14):4615–4636

    Article  CAS  PubMed  Google Scholar 

  • Koizumi JI, Monden Y, Aiba S (1985) Effects of temperature and dilution rate on the copy number of recombinant plasmid in continuous culture of Bacillus stearothermophilus (pLP11). Biotechnol Bioeng 27(5):721–728

    Article  CAS  PubMed  Google Scholar 

  • Kumar P et al (1991) Strategies for improving plasmid stability in genetically modified bacteria in bioreactors. Trends Biotechnol 9(1):279–284

    Article  CAS  PubMed  Google Scholar 

  • Kvint K et al (2003) The bacterial universal stress protein: function and regulation. Curr Opin Microbiol 6(2):140–145

    Article  CAS  PubMed  Google Scholar 

  • Kwanmin J (1989) Scale-down techniques for fermentation. Biopharm 2:30–39

    Google Scholar 

  • Lee SY (1996) High cell-density culture of Escherichia coli. Trends Biotechnol 14(3):98–105

    Article  CAS  PubMed  Google Scholar 

  • Lee JW et al (2012) Systems metabolic engineering of microorganisms for natural and nonnatural chemicals. Nat Chem Biol 8:536–546

    Article  CAS  PubMed  Google Scholar 

  • Lee SY, Kim HU, Chae TU, Cho JS, Kim JW, Shin JH, Kim DI, Ko YS, Jang WD, Jang YS (2019) Author correction: a comprehensive metabolic map for production of bio-based chemicals. Nat Catal 2(10):942–944

    Article  CAS  Google Scholar 

  • Leer RJ et al (1992) Structural and functional analysis of two cryptic plasmids from Lactobacillus pentosus MD353 and Lactobacillus plantarum ATCC 8014. Mol Gen Genet MGG 234(2):265–274

    Article  CAS  PubMed  Google Scholar 

  • Lin HY, Neubauer P (2000) Influence of controlled glucose oscillations on a fed-batch process of recombinant Escherichia coli. J Biotechnol 79(1):27–37

    Article  CAS  PubMed  Google Scholar 

  • Macaloney G et al (1994) Monitoring biomass and glycerol in an Escherichia coli fermentation using near-infrared spectroscopy. Biotechnol Tech 8(4):281–286

    Article  CAS  Google Scholar 

  • Matz G, Lennemann F (1996) On-line monitoring of biotechnological processes by gas chromatographic-mass spectrometric analysis of fermentation suspensions. J Chromatogr A 750(1–2):141–149

    Article  CAS  Google Scholar 

  • Mendoza-Vega O, Sabatie J, Brown S (1994) Industrial production of heterologous proteins by fed-batch cultures of the yeast Saccharomyces cerevisiae. FEMS Microbiol Rev 15(4):369–410

    Article  CAS  PubMed  Google Scholar 

  • Moser I, Jobst G, Urban GA (2002) Biosensor arrays for simultaneous measurement of glucose, lactate, glutamate, and glutamine. Biosens Bioelectron 17(4):297–302

    Article  CAS  PubMed  Google Scholar 

  • Muramatsu R et al (2002) Existence of β-methylnorleucine in recombinant hirudin produced by Escherichia coli. J Biotechnol 93(2):131–142

    Article  CAS  PubMed  Google Scholar 

  • Murphy T (1977) Design and analysis of industrial experiments, American Cyanamid Co., Bound Brook, NJ. Chem Eng USA DA 84(12):168–182. BIBL. 15 REF

    Google Scholar 

  • Naglak TJ, Keith MG, Omstead DR (1994) Validation of fermentation processes. BioPharm 7(6):28–36

    Google Scholar 

  • Neils C et al (2004) Combinatorial mixing of microfluidic streams. Lab Chip 4(4):342–350

    Article  CAS  PubMed  Google Scholar 

  • Neubauer P, Lin H, Mathiszik B (2003) Metabolic load of recombinant protein production: inhibition of cellular capacities for glucose uptake and respiration after induction of a heterologous gene in Escherichia coli. Biotechnol Bioeng 83(1):53–64

    Article  CAS  PubMed  Google Scholar 

  • Nielsen J, Keasling JD (2016) Engineering cellular metabolism. Cell 164(6):1185–1197

    Article  CAS  PubMed  Google Scholar 

  • Noorman HJ, Heijnen JJ (2017) Biochemical engineering’s grand adventure. Chem Eng Sci 170:677–693

    Article  CAS  Google Scholar 

  • Nordström K, Uhlin BE (1992) Runaway–replication plasmids as tools to produce large quantities of proteins from cloned genes in bacteria. Bio/Technology 10(6):661–666

    Google Scholar 

  • O’Sullivan LM et al (2001) Large scale production of cyclohexanone monooxygenase from Escherichia coli TOP10 pQR239. Enzym Microb Technol 28(2–3):265–274

    Article  Google Scholar 

  • Ondrey G (2013) 42nd Kirkpatrick award announced. Chem Eng 120(11):15

    Google Scholar 

  • Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell MD, Tai A, Main A, Eng D, Polichuk DR, Teoh KH, Reed DW, Treynor T, Lenihan J, Jiang H, Fleck M, Bajad S, Dang G, Dengrove D, Diola D, Dorin G, Ellens KW, Fickes S, Galazzo J, Gaucher SP, Geistlinger T, Henry R, Hepp M, Horning T, Iqbal T, Kizer L, Lieu B, Melis D, Moss N, Regentin R, Secrest S, Tsuruta H, Vazquez R, Westblade LF, Xu L, Yu M, Zhang Y, Zhao L, Lievense J, Covello PS, Keasling JD, Reiling KK, Renninger NS, Newman JD (2013) High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496(7446):528–532

    Article  CAS  PubMed  Google Scholar 

  • Pollard D et al (2001) Real-time analyte monitoring of a fungal fermentation, at pilot scale, using in situ mid-infrared spectroscopy. Bioprocess Biosyst Eng 24(1):13–24

    Article  CAS  Google Scholar 

  • Reinikainen P, Virkajärvi I (1989) Escherichia coli growth and plasmid copy numbers in continuous cultivations. Biotechnol Lett 11(4):225–230

    Article  CAS  Google Scholar 

  • Schaefer U et al (1999) Automated sampling device for monitoring intracellular metabolite dynamics. Anal Biochem 270(1):88–96

    Article  CAS  PubMed  Google Scholar 

  • Schmidt F (2005) Optimization and scale up of industrial fermentation processes. Appl Microbiol Biotechnol 68(4):425–435

    Article  CAS  PubMed  Google Scholar 

  • Spichiger-Keller UE (1997) Ion-and substrate-selective optode membranes and optical detection modes. Sensors Actuators B Chem 38(1–3):68–77

    Article  CAS  Google Scholar 

  • Thiry M, Cingolani D (2002) Optimizing scale-up fermentation processes. Trends Biotechnol 20(3):103–105

    Article  CAS  PubMed  Google Scholar 

  • Turner C, Rudnitskaya A, Legin A (2003) Monitoring batch fermentations with an electronic tongue. J Biotechnol 103(1):87–91

    Article  CAS  PubMed  Google Scholar 

  • Ulber R, Frerichs J-G, Beutel S (2003) Optical sensor systems for bioprocess monitoring. Anal Bioanal Chem 376(3):342–348

    Article  CAS  PubMed  Google Scholar 

  • Vaidyanathan S et al (1999) Monitoring of submerged bioprocesses. Crit Rev Biotechnol 19(4):277–316

    Article  CAS  Google Scholar 

  • Van de Merbel N (1997) The use of ultrafiltration and column liquid chromatography for on-line fermentation monitoring. TrAC Trends Anal Chem 16(3):162–173

    Article  Google Scholar 

  • Weickert MJ, Apostol I (1998) High-fidelity translation of recombinant human hemoglobin in Escherichia coli. Appl Environ Microbiol 64(5):1589–1593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weiss A (2016) Harnessing biotechnology: a practical guide. Chem Eng (New York) 123:38–43

    CAS  Google Scholar 

  • Whittaker MM, Whittaker JW (2000) Expression of recombinant galactose oxidase by Pichia pastoris. Protein Expr Purif 20(1):105–111

    Article  CAS  PubMed  Google Scholar 

  • Wolfbeis OS (2008) Fiber-optic chemical sensors and biosensors. Anal Chem 80(12):4269–4283

    Article  CAS  PubMed  Google Scholar 

  • Yang X (2010) Scale-up of microbial fermentation process. In: Manual of industrial microbiology and biotechnology, 3rd edn. American Society of Microbiology, Washington, DC, pp 669–675

    Google Scholar 

  • Zhuang KH, HerrgÃ¥rd MJ (2015) Multi-scale exploration of the technical, economic, and environmental dimensions of bio-based chemical production. Metab Eng 31:1–12

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. School of Biotechnology, KIIT Deemed to be University, Bhubaneswar, Odisha, India

    Lopamudra Ray & Vishakha Raina

  2. School of Law, KIIT Deemed to be University, Bhubaneswar, Odisha, India

    Lopamudra Ray

Authors
  1. Lopamudra Ray
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  2. Vishakha Raina
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Correspondence to Lopamudra Ray .

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Editors and Affiliations

  1. KIIT School of Biotechnology, KIIT University, Bhubaneswar, Odisha, India

    Mrutyunjay Suar

  2. Technology Business Incubator, KIIT University, Bhubaneswar, Odisha, India

    Namrata Misra

  3. Blvd, Hubbard, Meharry Medical College, Nashville, TN, USA

    Chandravanu Dash

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Ray, L., Raina, V. (2022). Scale-Up of Engineering Strain for Industrial Applications. In: Suar, M., Misra, N., Dash, C. (eds) Microbial Engineering for Therapeutics. Springer, Singapore. https://doi.org/10.1007/978-981-19-3979-2_14

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