Cover
Title Page
Title Page
Copyright
Volume I
1. Preface
2. Overview on Market Size of Bioproducts and Fundamentals of Cell Technology
  1. Biotechnology and global market size of bioproducts
  2. Cellular organization and membrane structure of three domains
3. Part I: Microbial Cell Technology
  1. 1.1 Basic bacterial growth and mode of fermentation
  2. 1.2 Basic fungal growth
  3. 1.3 Classical strain improvements and tools
  4. 1.4 Modern strain improvement and tools
  5. 1.5 Bioengineering and scale‐up process
  6. 1.6 New bioprocesses of fermentation
4. Part II: Applications of Microbial Fermentation to Food Products, Chemicals and Pharmaceuticals
  1. 2.1 Fermented dairy products
  2. 2.2 Fermented meat and fish products
  3. 2.3 Fermented vegetable and cereal products
  4. 2.4 Organic acids
  5. 2.5 Fermentation‐derived food and feed ingredients
  6. 2.6 Bacteriocins and bacteriophages
  7. 2.7 Enzymes
  8. 2.8 Biomass (SCP) and mushrooms
  9. 2.9 Functional foods and nutraceuticals
  10. 2.10 Alcoholic beverages
  11. 2.11 Other fermentation chemicals
  12. 2.12 Pharmaceuticals, growth promoters, and biopesticides
Volume II
1. Part III: Animal Cell Technology
  1. 3.1 Animal cell culture
  2. 3.2 Transgenic animal bioreactors
2. Part IV: Plant Cell Technology
  1. 4.1 Introduction
  2. 4.2 Plant tissue culture
  3. 4.3 Applications of plant tissue culture
3. Part V: Safety Issues of New Biotechnologies on Microbial, Animal, and Plant Cells
  1. 5.1 Introduction
  2. 5.2 Safety evaluation of novel foods and cell culture products
Index
End User License Agreement

List of Tables

Intro
1. Table 1 Fermentation biotechnology milestones and some recombinant proteins
2. Table 2 Some of recombinant biopharma products
3. Table 3 Different features in cells of bacteria, animal, and plant cells
Chapter 1
1. Table 1.1 The important bacterial family in biotechnological processes
2. Table 1.2 Some bacteria of biotechnological importance among 19 bacterial g...
3. Table 1.3 μ‐dependent product formation kinetics in continuous cultures
4. Table 1.4 Different strategies used to control the growth in a fed‐batch pr...
5. Table 1.5 Different parts of fermenter and its function
6. Table 1.6 Historically developed types and applications of bioreactors
7. Table 1.7 Advantages of immobilized enzymes and cells
8. Table 1.8 Some adsorbents for the immobilization of enzymes
9. Table 1.9 Applications of developed immobilized enzyme reactors
10. Table 1.10 Half‐lives of some immobilized enzymes
11. Table 1.11 Application and stability of various immobilized cells
12. Table 1.12 Examples of enzyme electrodes
13. Table 1.13 Comparison of Km and activation energy (kcal/g.mol) values of so...
14. Table 1.14 Temperature ranges of bacterial growth
15. Table 1.15 Some of recognized biotechnologically important fungi and molds
16. Table 1.16 Examples of analog resistant deregulated mutants which overprodu...
17. Table 1.17 Examples of auxotrophic mutants that overproduce primary metabol...
18. Table 1.18 Examples of chemical mutagens and their mode of action
19. Table 1.19 Some examples of restriction endonucleases, their origins, and s...
20. Table 1.20 Some examples of different vectors
21. Table 1.21 Advantages and disadvantages of the three cloning techniques
22. Table 1.22 Advantages and disadvantages of different expression hosts
23. Table 1.23 Comparison of next‐generation sequencing methods
24. Table 1.24 Milestones of CRISP‐Cas technology
25. Table 1.25 Major components and functions of CRISPR/Cas9.
26. Table 1.26 Applications of molecular thermodynamics in various fields of bi...
27. Table 1.27 The heat shock protein family of molecular chaperones
28. Table 1.28 Examples of bacterial quorum sensing controlled processes and tr...
29. Table 1.29 Models for studying QS in cooperative and competitive microbial ...
30. Table 1.30 Solubilities of substrates and metabolites in water at 25 °C
31. Table 1.31 Effect of substrate and cell yield on oxygen requirement and hea...
32. Table 1.32 Heat production during the continuous culture of microorganisms ...
33. Table 1.33 Estimated operating costs for biomass production from different ...
34. Table 1.34 Flow characteristics of three types of pressure‐driven membrane ...
35. Table 1.35 Two‐phase aqueous extractions of enzymes from microbial cells*
36. Table 1.36 Different methods and characteristics of chromatographic process...
37. Table 1.37 Type of data required from laboratory and pilot experiments for ...
38. Table 1.38 Scale factors in translation of pilot plant data into production
39. Table 1.39 Basic process control parameters that can be measured in ferment...
40. Table 1.40 Some affinity tags of proteins and peptides used for purificatio...
Chapter 2
1. Table 2.1 Lactic acid bacteria and predominant species
2. Table 2.2 Contributions of lactic acid bacteria as natural ingredients, hea...
3. Table 2.3 Plasmid encoded functions of lactic acid bacteria
4. Table 2.4 Genetic transfer systems in lactic acid bacteria
5. Table 2.5 Cloning and expression of heterologous genes in lactic acid bacte...
6. Table 2.6 Possible targets of genetic engineering in modifying starter cult...
7. Table 2.7 Classification of various fermented sausages
8. Table 2.8 Classification of fermented sausages in Europe (non–heat treated)
9. Table 2.9 Bacteria used as starter cultures in meat, poultry, and fish prod...
10. Table 2.10 Some bacteria investigated for their potential use as starter cu...
11. Table 2.11 Fish sauces
12. Table 2.12 Fish pastes and their ingredients
13. Table 2.13 Key characteristics of the four genera of acetic acid bacteria c...
14. Table 2.14 Comparison of acetic acid productivity between two transformants...
15. Table 2.15 Raw materials used in lactic acid production by fermentation and...
16. Table 2.16 Bacteria capable of producing vanillin from ferulic acid.
17. Table 2.17 World production and applications of amino acids for the food an...
18. Table 2.18 Overview of yield obtained with different amino acids production...
19. Table 2.19 Overview of metabolic engineering strategies to improve amino ac...
20. Table 2.20 Some consumer and industrial applications of gums
21. Table 2.21 Sales of major food‐approved polysaccharides
22. Table 2.22 Microbial polysaccharides related to the food industry
23. Table 2.23 Global PHA producers and their substrates.
24. Table 2.24 Bacteriocins of bacteria and archea
25. Table 2.25 Pros and cons of the use of bacteriophages and phage lytic prote...
26. Table 2.26 Applications of important commercial food enzymes
27. Table 2.27 Some properties and applications of commercial lactases
28. Table 2.28 Some properties and applications of commercial lipases
29. Table 2.29 Few important therapeutic enzymes in medicine
30. Table 2.30 Source organisms and substrate used for the production of bacter...
31. Table 2.31 Substrates for microbial protein production
32. Table 2.32 Comparative analysis of various biomass products
33. Table 2.33 Industrial establishments involved in SCP production
34. Table 2.34 Economics of the five SCP processes versus soymeal and fish meal
35. Table 2.35 Examples of functional food components
36. Table 2.36 Properties and benefits of good probiotic strains
37. Table 2.37 Other potential applications of probiotics
38. Table 2.38 Non‐digestible oligosaccharides with bifidogenic functions comme...
39. Table 2.41 World production of wine and annual per capita consumption in 20...
40. Table 2.39 World beer production (2011) in different countries
41. Table 2.40 Per capita consumption of beer in different countries (2015–2016...
42. Table 2.42 Some targeted desirable characteristics of a wine yeast that may...
43. Table 2.43 Annual fuel ethanol production (millions of US. liquid gallons p...
44. Table 2.44 Theoretical ethanol yield from different biomass feedstocks
45. Table 2.45 Fermentation ethanol from feedstocks
46. Table 2.46 Chemical and physical properties of gasoline, diesel, butanol an...
47. Table 2.47 Butanol fermentation from starch‐based substrates
48. Table 2.48 Comparisons of ABE fermentation from lignocellulosic materials
49. Table 2.49 Improvement strategies for biobutanol production
50. Table 2.50 Typical results of microbial production of diols in different pr...
51. Table 2.51 Some typical yields of biodiesel from different crops
52. Table 2.52 Biogas composition (%) from different substrates by anaerobic di...
53. Table 2.53 Biomethane production of selected lignocellulosic biomass.
54. Table 2.54a Comparison of production rate of biological H₂ in different pro...
55. Table 2.54bAdvantages and disadvantages of biohydrogen production processes.
56. Table 2.55 Fermentative hydrogen production from various biomass
57. Table 2.56a Classification of antibiotics based on chemical structure and me...
58. Table 2.56b Some of common commercial antibiotics
59. Table 2.57 Overview of various discovery platforms for antibacterial drugs
60. Table 2.58 Some examples of natural products (NP), semisynthetic natural pr...
61. Table 2.59 Production of other antibiotics and productivity using fermentat...
62. Table 2.60 Penicillin production and strain development by mutagenesis and ...
63. Table 2.61 Types and effectiveness of penicillin (PEN) including natural an...
64. Table 2.62 Antibiotic use for growth promotion in livestock production
65. Table 2.63 Antimicrobial classes and products on the basis of importance of...
66. Table 2.64 The estimated numbers of new cases and deaths for each common ca...
67. Table 2.65 The top ten best‐selling cancer drugs of 2018 (in terms of reven...
68. Table 2.66 Lists of FDA‐approved anticancer drugs from 1949 to 2014
69. Table 2.67 Some known microbial anti‐tumour compounds
70. Table 2.68 Examples of biopharmaceutical compounds produced by applying yea...
71. Table 2.69 Major steroids and their physiological functions
72. Table 2.70 Some enzymes used for steroid biotransformation and their functi...
73. Table 2.71 Microbial production of steroidal intermediates from natural ste...
74. Table 2.72 Improved statin production through chemical and physical mutagen...
75. Table 2.73 Milestone of commercial development and discovery on biopesticid...
Chapter 3
1. Table 3.1 Large‐scale manufacturing facilities for the production of viral ...
2. Table 3.2 Different types of microcarriers commercially available
3. Table 3.3 Comparisons of batch, fed‐batch and continuous (perfusion) of cel...
4. Table 3.4 Some examples of industrial‐scale animal cell suspension culture
5. Table 3.5 Therapeutic monoclonal antibodies approved or under review in the...
6. Table 3.6 Milestones of vaccine development
7. Table 3.7 Composition of the pertussis component of selected vaccines
8. Table 3.8 Some licensed polysaccharide and conjugate vaccines by 2016*
9. Table 3.9 Advantages and disadvantages of next generation vaccines platform...
10. Table 3.10 Licensed and promising vaccine adjuvants
11. Table 3.11 Few types of micro‐and nanoparticles studied for antigen deliver...
12. Table 3.12 Comparison between traditional and reverse vaccinology
13. Table 3.13 Some of commercial hepatitis vaccines produced by different comp...
14. Table 3.14 Completed phase II and III human HIV‐1 vaccine trials*
15. Table 3.15 Package inserts and manufacturers for some US‐licensed vaccines ...
16. Table 3.16 COVID‐19 candidate vaccines undergoing clinical trials by 2020
17. Table 3.17 Milestones of some successful transgenic animals and fishes
Chapter 4
1. Table 4.1 Milestone of plant tissue culture
2. Table 4.2 Advantages and disadvantages of plant tissue culture
3. Table 4.3 Applications of embryo plant tissue culture
4. Table 4.4 Factors affecting viability of plant cells frozen for cryopreserv...
5. Table 4.5 Some useful plant variants generated through somaclonal variation...
6. Table 4.6 Some successful asymmetric protoplast fusion in different plant f...
7. Table 4.7 Summary of the applications, advantages and disadvantages of soma...
8. Table 4.8 Substances reported from plant cell cultures
9. Table 4.9 Some known commercial natural products and heterologous proteins ...
10. Table 4.10 Some selected secondary metabolites produced by wild‐type HR cul...
11. Table 4.11 Some selected secondary metabolites and recombinant proteins pro...
12. Table 4.12 Some selected phytoremediation of various pollutants by wild or ...
13. Table 4.13 Other biotransformation for secondary plant metabolites with pot...
14. Table 4.14 Composition of media most frequently used*
15. Table 4.15 Classification of plant cell bioreactors for production of prote...
16. Table 4.16 Transformation advantages of chloroplast genome over nuclear gen...
17. Table 4.17 Many vaccine antigens and biopharmaceuticals produced by enginee...
18. Table 4.18 Commercially grown genetically modified crops and food species
19. Table 4.19 Global area of GM crops in 2017 by country (million hectares)**
20. Table 4.20 Top ten and rest countries which granted food, feed and cultivat...
21. Table 4.21 Application of CRISPR based genome editing approach in plants fo...
Chapter 5
1. Table 5.1 Summary of criteria used in the safety evaluation of novel foods ...
2. Table 5.2 Some areas of safety consideration in the regulation of foods, fo...
3. Table 5.3 Regulatory framework for food, food products, feed products deriv...
4. Table 5.4a Some of the transgenic animals with potential commercial applica...
5. Table 5.4b The sequence availability of the GM animals listed in Table 5.4a.
6. Table 5.5 Some of pros and cons for genetically modified animals and crops
7. Table 5.6 Safety consideration and regulation of genetically modified foods...
8. Table 5.7 Summary of several detection methods for GMO* products

List of Illustrations

Intro
1. Figure 1 Concept of cell culture technology derived from microbes, animals, ...
2. Figure 2 (a) Scheme of microbial bioproducts except for fermented foods and ...
3. Figure 3 A phylogenetic tree based on rRNA data, showing the separation of b...
4. Figure 4 Fluid mosaic model for cell membrane (Source: http://www.biology.ar...
5. Figure 5 Concept of three life domains based on rRNA data, showing the separ...
Chapter 1
1. Figure 1.1 The graph showing the principle of a substrate limited fed‐batch ...
2. Figure 1.2 Simplified schematic illustration of different culture methods. (...
3. Figure 1.3 Types of submerged‐culture fermenter. (a) Stirred‐tank fermenter,...
4. Figure 1.4 Basic immobilized enzyme or cell reactor types.
5. Figure 1.5 Representation of wave bioreactor (Source: OpenWAVE25). (See inse...
6. Figure 1.6 Sexual reproduction cycle in yeast
7. Figure 1.7 Pathway and control of lysine production in auxotrophic mutant of...
8. Figure 1.8 Outline of the three general strategies of gene cloning.
9. Figure 1.9 Scheme of cloning a foreign chromosomal DNA fragment using a vect...
10. Figure 1.10 Outline structure of the cloning vector pUC18 with some of the r...
11. Figure 1.11 Simplified scheme of using reverse transcriptase to convert mRNA...
12. Figure 1.12 Principles of the polymerase chain reaction (PCR).
13. Figure 1.13 A brief history of RNAi evolution (www.thermofisher.com/kr/ko/ho...
14. Figure 1.14 RNAi mechanism. (i) The entry of long double‐stranded RNA such a...
15. Figure 1.15a Mechanism of CRISPR/Cas immunity divided into three stages. Sta...
16. Figure 1.15b Mechanism of CRISPR immunity in all three types of CRISPR/Cas s...
17. Figure 1.15c The structural features of CRISPR. The repeat sequences with co...
18. Figure 1.16 Biological and crystal structure of Cas‐9. The Cas9 protein is r...
19. Figure 1.17 Different steps involved in synthesis of stable protein (adapted...
20. Figure 1.18 Protein folding inside the cell. A new protein is synthetized at...
21. Figure 1.19 The rational/semi‐rational design (site‐directed mutagenesis) an...
22. Figure 1.20 Reaction scheme for the Kemp elimination of 5‐nitrobenzisoxazole...
23. Figure 1.21 (a) A microarray may contain thousands of “spots”. Each spot con...
24. Figure 1.22 (a‐c) Illustration of the overlap between metabolic engineering ...
25. Figure 1.23 Contribution and overlap of systems/synthetic biology to metabol...
26. Figure 1.24 Model of quorum sensing in Vibrio fischeri. Permission from Poph...
27. Figure 1.25 General process scheme for upstream and downstream fermentation....
28. Figure 1.26 Resistance to oxygen transfer from the air bubble to a microbial...
29. Figure 1.27 Factors contributing to and phenomena affected by heat effects i...
30. Figure 1.28 Correlation of heat production Y_Δ and biomass yield Y_s on d...
31. Figure 1.29 General schemes of protein recovery operation through sequences ...
32. Figure 1.30 A process flow sheet for product recovery.
33. Figure 1.31 Separation methods based on physico‐chemical properties of parti...
34. Figure 1.32 Flow processes in the production of recombinant chymosin.
35. Figure 1.33 Scale‐up requiring a highly interdisciplinary task, concepts and...
36. Figure 1.34 Scaling fermentation vessels by the 1:10 ratio method.
37. Figure 1.35 RITE Bioprocess®, an innovative growth‐arrested bioprocess devel...
38. Figure 1.36 RITE bioprocess for producing biofuels and other green chemicals...
39. Figure 1.37 Overall process set‐up of fully integrated reactive extraction i...
40. Figure 1.38 Bioprocessing approaches for the conversion of lignocellulosic b...
Chapter 2
1. Figure 2.1 Basic steps of most cheese varieties (e.g. Cheddar).
2. Figure 2.2 Dynamic nature of cheese flavor development. Source: Steele et al...
3. Figure 2.3 Secondary biochemical changes during cheese ripening.
4. Figure 2.4 Transformation of fatty acids.
5. Figure 2.5 Catabolic pathways of lactose and galactose by lactococci: 1, the...
6. Figure 2.6 Citrate metabolism in lactic acid bacteria.
7. Figure 2.7 General proteolytic system of lactic acid bacteria in cheese.
8. Figure 2.8 Overview of the putative functions of plasmid‐encoded genes in L....
9. Figure 2.9 The overall process of chymosin production using recombinant K. l...
10. Figure 2.10 Flowchart for soy sauce manufacture.
11. Figure 2.11 Flowchart for rice–miso manufacture.
12. Figure 2.12 Pathways from glucose to fumaric acid. Source: Xu et al., 2012....
13. Figure 2.13 Oxidative formation of methyl ketones by Penicillium roqueforti....
14. Figure 2.14 Production of diacetyl from citrate.
15. Figure 2.15 Oxidative conversion of ricinoleic acid into γ‐decalactone by Ca...
16. Figure 2.16 Highest reported value for each terpenoid class produced by diff...
17. Figure 2.17 Vanillin production by eugenol degradation by Corynebacteirum sp...
18. Figure 2.18 Schematic representation of the non‐β‐oxidative pathway for conv...
19. Figure 2.19 Construction of plasmids pBB1 containing genes from Pseudomonas ...
20. Figure 2.20 Production of 10–15 DE syrup by thermostable α‐amylase.
21. Figure 2.21 Process flowchart for dextrose production.
22. Figure 2.22 Schematic diagram of the production of HFCS 55 and HFCS 90 from ...
23. Figure 2.23 Conversion of D‐glucose to 2‐KGA by way of (1) two‐stage ferment...
24. Figure 2.24 Summary of major natural pigment classes in the market and their...
25. Figure 2.25 Fermentation process for the production of microbial xanthan.
26. Figure 2.26 Schematic representation of the alginate biosynthetic steps in A...
27. Figure 2.27 Structure of nisin.
28. Figure 2.28 Structure of pediocin PA‐1.
29. Figure 2.29 Schematic overview of the suggested machinery for production of ...
30. Figure 2.30 Global versus Chinese enzyme market in 2010.
31. Figure 2.31 General scheme for enzyme production and downstream processing....
32. Figure 2.32 Flow diagram of stages in the production of Agaricus bisporus.
33. Figure 2.33 Mechanisms of immunomodulation by beneficial microbes. Probiotic...
34. Figure 2.34 Restorative strategies for dysbiosis. Probiotics may be administ...
35. Figure 2.35 Schematic outline of the brewing process.
36. Figure 2.36 Structure of humulone and isomerization.
37. Figure 2.37 Schematic outline of wine making.
38. Figure 2.38 Formation of ethyl carbamate.
39. Figure 2.39 Schematic operation of sake production.
40. Figure 2.40 Classification of biofuels. Source: Nigam and Singh, 2011.
41. Figure 2.41 Scheme for a continuous flow fermentation process of bioethanol....
42. Figure 2.42 Timeline of notable events and advances in butanol fermentation ...
43. Figure 2.43 Pathway of acetone–butanol–ethanol (ABE) fermentation by clostri...
44. Figure 2.44a A representative schematic diagram of fermentative butanol prod...
45. Figure 2.44b Common (i) pretreatment methods, (ii) detoxification methods, (...
46. Figure 2.45 Condensation of dehydrated bioethanol (100% anhydrous state) to ...
47. Figure 2.46 Major routes for bioproduction of diols from different feedstock...
48. Figure 2.47 Natural (a) and engineered metabolic pathways (b–d) enabling bio...
49. Figure 2.48 Some important derivatives of 2,3‐butanediol and their potential...
50. Figure 2.49 The metabolic pathways for 2,3‐butanediol synthesis in bacteria....
51. Figure 2.50 World biodiesel production and capacity. Source: Biodiesel 2020:...
52. Figure 2.51 Cultivation of microalgae species in waste‐water and photo‐biore...
53. Figure 2.52a The scheme of the anaerobic digestion plant (www.globalmethane....
54. Figure 2.52b Schematic representation of the sustainable cycle of anaerobic ...
55. Figure 2.53 Process stages of the conversion of lignocellulosic biomass to b...
56. Figure 2.55 Biohydrogen gas production through in vitro artificial enzymatic...
57. Figure 2.55 Schematic of (a) a single and (b) dual‐chambered microbial elect...
58. Figure 2.56a Roadmap from microalgae to hydrogen. Source: Wang and Yin, 2018...
59. Figure 2.56b The production of biohydrogen in microalgae. In the alga Chlamy...
60. Figure 2.57 Antibiotic targets and mechanisms of resistance. Source: Wright,...
61. Figure 2.58 Early stages of antibiotic discovery from microbial product libr...
62. Figure 2.59 Outline diagram of current penicillin production by fed‐batch su...
63. Figure 2.60 Chemical structures of different classes of penicillins. Example...
64. Figure 2.61 Schematic overview of the penicillin biosynthetic pathway. ACVS,...
65. Figure 2.63 Global antimicrobial use in food animals. (a) Major users of ant...
66. Figure 2.63 Structures of some microbial anticancer compounds such as mithra...
67. Figure 2.64 Structures of different type II polyketides synthases (PKSs) pro...
68. Figure 2.65 Mode of action of doxorubicin (DXR) inside the cancer cell. Doxo...
69. Figure 2.66 Physical and functional map of the daunorubicin and doxorubicin ...
70. Figure 2.67 Overall scheme used for enhanced production of daunorubicin and ...
71. Figure 2.68 Schematic representation of genes involved in regulation of daun...
72. Figure 2.69 Four axes of yeast's contribution to cancer research. (a) Elucid...
73. Figure 2.70 Yeast‐based cancer studies. Top: Synthetic lethality interaction...
74. Figure 2.71 Editing of BGCs based on CRISPR/Cas9 strategies. (a) HDR‐mediate...
75. Figure 2.72 Classification of the microbial bioprocesses for steroid synthes...
76. Figure 2.73 Chemical structures of relevant steroidal compounds containing t...
77. Figure 2.74 Scheme of the rational construction of mycobacterial strains pro...
78. Figure 2.75 Chemical structure of statins and the enzyme substrate HMG‐CoA. ...
79. Figure 2.76 The HMG‐CoA reductase pathway, which is blocked by statins via i...
80. Figure 2.77 Biosynthesis pathway of lovastatin. Source: Subhan et al., 2016....
81. Figure 2.78 Chemical structures of lovastatin acid, monacolin J acid, and si...
Chapter 3
1. Figure 3.1 (a) Roller bottles Source: Amy T. Lang/Corning, Inc. and (b) mult...
2. Figure 3.2 MDCK cells grown in serum‐free medium (MDSS2N with 0.45% plant ex...
3. Figure 3.3 Schematic representation of the hybridoma technology for producin...
4. Figure 3.4 Scheme of downstream process for manufacturing recombinant protei...
5. Figure 3.5a Strains development of animal cell cultures by several methods i...
6. Figure 3.5b Genetic engineering scheme of animal cell culture for recombinan...
7. Figure 3.6a Steps in the production and selection of monoclonal antibody/sec...
8. Figure 3.6b Overview of mABs production. Source: European‐Molecular‐Biology ...
9. Figure 3.7 Typical downstream process for monoclonal antibody production....
10. Figure 3.8 Schematic overview of the different strategies used to generate b...
11. Figure 3.9 The convention vaccine development using two methods in general....
12. Figure 3.10 Comparison between production of glycoconjugates through (a) che...
13. Figure 3.11 Schematic illustration in the making of a DNA vaccine against We...
14. Figure 3.12 GenePro® strategic vaccine approach for the induction of therape...
15. Figure 3.13 Induction scheme of cellular and humoral immunity by DNA vaccine...
16. Figure 3.14 Representative structures of various nanoparticles for drug deli...
17. Figure 3.15 Schematic diagram summarizing the pathway of vaccine development...
18. Figure 3.16 Summary of the reverse vaccinology protocol applied to Campyloba...
19. Figure 3.17 The mRNA‐based strategy for Zika vaccine by cloning of genes for...
20. Figure 3.18 The production scheme of recombinant hepatitis B vaccine.
21. Figure 3.19a HIV retrovirus schematic of (a) cell infection, virus productio...
22. Figure 3.19c Steps of retrovirus replication cycle (With permission of wikip...
23. Figure 3.20 Somatic‐cell nuclear transfer.
Chapter 4
1. Figure 4.1 Basic procedure for obtaining a culture of plant tissue.
2. Figure 4.2The protocol and procedure for plant micropropagation of seed.
3. Figure 4.3 General steps involved in callus culture.
4. Figure 4.4 The common protocol for plant protoplast isolation.
5. Figure 4.5 General cryopreservation method of plant cell cultures.
6. Figure 4.6a Basic procedure for obtaining somatic hybrids from normal cell p...
7. Figure 4.6b Basic procedure for obtaining somatic hybrids by either symmetri...
8. Figure 4.7 Production of novel interspecific and intergenic hybrid pomato be...
9. Figure 4.8 Large‐scale production scheme of shikonin by L. erythrorhizon cel...
10. Figure 4.9 Pathway for in vivo production of taxadiene and 5‐α‐hydroxytaxadi...
11. Figure 4.10a,b (a) Representative multistep semisynthesis of paclitaxel (R =...
12. Figure 4.10 (Continued)
13. Figure 4.11 Artemisinin biosynthesis pathway occurs in the glandular trichom...
14. Figure 4.12 Engineering of E. coli for the biosynthesis of artemisinic acid ...
15. Figure 4.13a Production of artemisinic acid or β‐farnesene by engineered yea...
16. Figure 4.13b Sanofi industrial semi‐synthesis of artemisinin by large‐scale ...
17. Figure 4.14 Scheme on de novo production of resveratrol from glucose or etha...
18. Figure 4.15 The ecy of algal biodiesel production.
19. Figure 4.16 Plant bioreactor system via protein compartmentation within a pl...
20. Figure 4.17 Research network in elemental and functional research areas of H...
21. Figure 4.18 Global area of GM crops from 1996 to 2017 (million hectares)....
22. Figure 4.19 Global map of GM crop countries and mega‐countries in 2017 (*18 ...
23. Figure 4.20 Adoption status of GM crops in the US during 1996–2017. Data for...
24. Figure 4.21 Status of approved GM crops used in food, feed, processing, and ...
25. Figure 4.22 Contribution of GM crops to food security, sustainability and cl...

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Library of Congress Cataloging‐in‐Publication Data

Names: Lee, Byong H., author.

Title: Advanced fermentation and cell technology / Byong H. Lee,

SportBiomics, CA, USA and Heilenex Pharma Inc., Toronto, Canada, Kangwon National

University, Chuncheon, South Korea, Jiangnan University, Wuxi, China, McGill University and

AAFC, Quebec, Canada.

Description: Hoboken, NJ, USA : Wiley‐Blackwell, 2022. | Includes

bibliographical references and index.

Identifiers: LCCN 2020026477 (print) | LCCN 2020026478 (ebook) | ISBN

9781119042761 (cloth) | ISBN 9781119042785 (adobe pdf) | ISBN

9781119042778 (epub)

Subjects: LCSH: Fermentation. | Industrial microbiology.

Classification: LCC TP505 .L44 2021 (print) | LCC TP505 (ebook) | DDC

660/.28449–dc23

LC record available at https://lccn.loc.gov/2020026477

LC ebook record available at https://lccn.loc.gov/2020026478

Cover Design: Wiley

Cover Images: Tubular bioreactors filled green algae fixing CO2 © Santiago Urquijo / Getty Images, Cultures growing on Petri dishes © WLADIMIR BULGAR/SCIENCE PHOTO LIBRARY / Getty Images, CAR T cell immunotherapy, illustration © KEITH CHAMBERS/SCIENCE PHOTO LIBRARY / Getty Images, Bison or Aurochs in winter season in their habitat © danm / Getty Images, CoronaVirus CopySpace © BlackJack3D / Getty Images, illustration 3d DNA Spin Futuristic digital background, Abstract background for Science and technology © Jackyenjoyphotography / Getty Images

Preface

The term fermentation derived from the Latin verb fevere (boil) used by humans for the production of food and beverages since the Neolithic age is the oldest of all biotechnological processes. The fermentation process used in the production of antibiotics, alcohol, bread, vinegar and other food or industrial products differs from respiration in that organic substances rather than molecular oxygen are used as electron acceptors. After successful microbial fermentation processes on microbial cells (biomass), microbial enzymes, microbial metabolites including antibiotics, and other fermented foods, currently more than 3500 different fermented foods are consumed by humans worldwide. The potential of fermentation techniques was dramatically increased in the late 1960s and 1970s through achievements in molecular genetics, cell fusion, and enzyme technology. However, additional completely novel, powerful techniques such as genetic engineering via recombinant DNA technology in 1973 and hybridoma technology (monoclonal antibody) in 1975 were responsible for the current biotechnology boom.

In genetic engineering, a known gene is inserted into a microbial, animal, or plant cell in order to achieve a desired trait for the overproduction of target compounds, but microorganisms have played a major role in the development of biotechnology. This is due to the rapid growth of microbes, cheap growth media, massive diversity in the metabolite types and easy of genetic manipulation. However, mass culture of animal cell lines is also important to manufacture viral vaccines and other therapeutic recombinant products such as enzymes, hormones, immunologicals (monoclonal antibodies, interleukins, lymphokines, etc), and anticancer agents. Mammalian cells cultivated in bioreactors have surpassed microbial systems for producing therapeutic recombinant proteins because of their capacity for proper protein folding, assembly and post‐translational modification. Major therapeutic recombinant proteins are successfully commercialized, but expensive animal free media, cost of production in large scale with low yield (the tens‐of‐milligrams/liter), microbial contamination, and gene regulation are the important issues to be resolved. Other cell culture research is also underway to produce such complex therapeutic proteins in insect cell (baculovirus) or in higher plants. Molecular biopharming using transgenic animals such as goat and pig for rDNA proteins have also successfully commercialized.

Fermentation technology for the production of compounds that find application in food, biochemical, biomaterial, bioenergy, pharmaceutical sectors encompasses a broad field, not only including (1) conventional microbial and enzyme systems, (2) genetic and metabolic engineering, along with systems biology/synthetic biology, and genome editing, but also including (3) mammalian cell and plant cell systems. Despite a long history of fermentation processes for generations, the requirement for sustainable production of bioenergy and biomaterials is also demanding innovation and development of novel fermentation concepts. Continued introduction of new technology in cell culture systems demands innovation in new bioreactor process development and scale up processes for cell factory potential.

This book reflects this transition from traditional fermentation technology to new cell fermentation technology, that provides equal emphasis on microbial, mammalian as well as plant cell technologies for new and improved processes and products in today's biochemical process industry.

Currently two fermentation textbooks available on the market (1999) are outdated and do not deal with current progress in fermentation and cell culture technologies and commercial recombinant bioproducts. Most other edited volumes are the work of multiple contributors and normal didactic criteria for explanation of evolving new techniques and applications are lacking. Experience in teaching this subject has made clear that the basic concepts and essential features have not been covered in a typical science curriculum. The primary objective of writing this book is to relate the food fermentation and cell culture biopharmaceutical actives using different expression hosts. Product diversity makes fermentation technology a multi ‐disciplinary expertise associated with microbiology, organic chemistry, biochemistry, and molecular biology. Remarkable advances in these areas will help to lift people out of wretched and empower them with new knowledge. The subject matter is divided into Part V, including microbiology, biotechnology, molecular biology, biochemical engineering, and global market size of bioproducts, and their applications.

Part I covers microbial cell technology and culture tools (including classical strain improvements and tools) and modern strain improvement and tools (genome shuffling, recombinant DNA technology, RNA interference (RNAi) and CRISPR)/Cas technology for genome editing; also includes molecular thermodynamics for biotechnology, protein engineering, genomics, proteomics and bioinformatics, systems/synthetic biology and metabolic engineering, quorum sensing and quenching. Other bioengineering and scale‐up processes and new bioprocesses of fermentation such as growth‐arrested bioprocess, integrated bioprocess, and consolidated bioprocessing (CBP) are included.

Part II deals applications of microbial fermentation to food products (dairy, meat/fishes, vegetable/cereals), organic acids, food ingredients, chemicals, and pharmaceuticals. Food products/ingredients included flavors and amino acids, sweeteners, vitamins and pigments, microbial polysaccharides/biopolymers, bacteriocins and bacteriophages, enzymes, biomass (SCP)/mushrooms, functional foods and nutraceuticals such as probiotics and prebiotics, and microbiome. Others included alcoholic beverages and other fermentation chemicals (bioethanol, biobutanol/biobutandiol, biodiesel, biomethane, biohydrogen). In final section, pharmaceuticals such as antibiotics, antibiotic growth promoters, antitumor drugs, steroids/statins, and biopesticides included.

Part III covers (i) animal cell technology including animal cell culture, bioprocessing, strain development, applications (monoclonal antibodies, different vaccines (DNA vaccines, edible vaccines, zika vaccines, hepatitis vaccines, HIV vaccines, COVID 19 vaccines), and (ii) transgenic animal bioreactors, and applications in animals and fishes, etc. Part IV on plant cell technology covered plant tissue and cell culture and applications, bioreactor types (seed‐based bioreactor, plant cell suspension bioreactor, hairy root bioreactor, chloroplast bioreactors) and modern plant breeding or biotech/GM crops and their applications.

Finally, Part V deals with safety issues of new biotechnologies on microbial, animal, and plant cells.

This book aims to give readers, general science students, researchers, and industrial practitioners as well as instructors, an overview of the essential features of advanced fermentation and cell culture technology. I would like to thank my students, post‐docs, and former colleagues at McGill University (Canada), Jiangnan University (China) and Kangwon National University (Korea), who, for the past 37 years, have helped and suggested me in teaching this subject course.

Among the over hundres of my former graduate students and post‐docs, I would like to dedicate this book specifically to my beloved former students, Dr. Young J. Choi and Dr. Marcio Belem in Montreal, whom both passed away suddenly.

Last but not least, I must thank my wife Young for her love and encouragement, together with the patience of my sons, Edward and his family (wife Maria, son Maxim) in Toronto and David and his family (wife Ronit, daughter Romy) in Santa Monica, California during the preparation of this volume.

September, 2021

Byong H. Lee

Toronto, Canada

Advanced Fermentation and Cell Technology

Advanced Fermentation and Cell Technology

Preface