Index 2013 Bioprocess-Engineering

Index
absolute filtration, 204 anaerobic fermentation, 58, 59,

acceleration phase, 106 62, 66, 142
activation energy of thermal death, anaerobic respiration, 22, 58, 59
192 anaplerotic reactions, 67
adaptive enzyme, 45, 48, anticodon, 41
106 aqueous two phase extraction, 229
adenosine phosphates, 34 archaebacteria, 9
ADP, 34, 54, 55, 57, 58, 61, 62, archea, 8, 9, 10, 15, 20
64, 65, 66, 68, 70 Arrhenius form, 192
adsorption, 87 ATP, 31, 34, 54, 55, 57, 58, 61,
adsorption isotherms, 229 62, 64, 65, 66, 67, 68,
aerobic respiration, 57, 58, 59, 74, 70, 72
98, 141, 142 axial dispersion, 200, 201, 202,
aerotolerant anaerobes, 59 203
affinity chromatography, 231
air sterilisation, 189, 190, 203 β-oxidation, 31, 62, 72
aldoses, 26 fats, 68–71
alkaline solution, 99 balanced growth, 109
alkanes, 71 batch culture, 11, 97, 98, 101,
allolactose, 47 102, 103, 104, 112, 123,
allosteric enzyme, 83 124, 140, 161
amino acids, 3, 21, 22, 31, 32, 33, batch enzyme reactor, 86
38, 42, 99, 100, 101, 113, batch filtration, 213–14
190, 231 batch process
AMP, 34, 48, 54 bubble density distribution,
amylases, 4, 30, 75 103
amylopectin, 28, 29 dependence of growth rate on
amylose, 28 substrate concentration,
anabolic pathways, 71–3 112–15
anabolism, 53 design equations, 101–16
235
Published by Woodhead Publishing Limited, 2013

Index
flask cultures in shaker oxygen transfer, 185–6

incubator on the lab bench, power requirements, 185
104 shear stress, 186
instrumented laboratory stirred constant mixing, 180–2
tank reactor, 105 flow regime, 182
microbial growth rate, 102–11 oxygen transfer, 181
batch growth curves, 110 power requirements, 180–1
characteristic microbial shear stress, 181–2
growth phases, 107 constant oxygen transfer rate,
effect of substrate 173–80
concentration on specific flow regime, 179–80
growth rate, 113 geometrically similar vessels,
exponential growth of single 175
bacterial cell, 107 mixing, 176–8
rate of substrate utilisation and power requirements, 174–6
product formation, 115–16 shear stress, 178–9
batch sterilisation, 193–9, 200, constant shear stress, 182–6
202 flow regime, 184–5
binomial nomenclature, 10 mixing, 184
biocatalysts, 75–96 oxygen transfer, 183–4
enzyme kinetics with inhibition, power requirements, 183
78–84 biotechnology, 1
enzyme kinetics with no biotransformation, 75
inhibition, 76–8 BIOX process, 4
enzyme reactors with bubble density distribution, 102
immobilised enzymes, buffering capacity, 22, 100
86–95
enzyme reactors with soluble CAP, 48
enzymes, 84–6 carbohydrates, 18, 21, 26–30, 31,
biodiesel, 20 59, 62, 71, 130, 148
bioprocess cellulose, 29
asepsis and sterility, 189–207 D-glucose conversion from
air filter sterilisation, 203–7 straight chain to pyranose
media and equipment heat form, 28
sterilisation, 190–203 families of D-aldoses and
bioprocess engineering, 1–6 ketoses, 27
bioprocess scale up, 171–87 starch, 29
constant flow regime, 185–7 sucrose, 28
mixing, 186 carbon, 99
236

Index
carbon metabolism, 53–74 centrifugation, 109, 213, 216,

anabolic pathways, 71–3 217, 219
fatty acid synthesis, 71–3 chemo-autotrophs, 19, 20
gluconeogenesis, 73 chemo-heterotrophs, 53,
catabolic pathways, 59–71 59, 98
β-oxidation of fats, 68–71 chromatography, 209, 211, 212,
glycolysis, 59–62 220, 229–32
schematic of β-oxidation of CLEA, 87
fats, 69 co-repressor, 47
schematic of glycolysis, 60 CoA, 35
schematic of tricarboxylic coagulation, 217
acid cycle, 63 codon, 41
tricarboxylic acid cycle, 62–8 coenzyme A, 35
energy generation, storage and competitive inhibition, 79, 80, 82
transfer, 54–9 complex media, 130
active groups NAD, FAD and compressibility, 215
CoQ reduction, 56 concentration polarisation, 226
electron transport chain or constitutive enzyme, 45, 48
oxidative phosphorylation, continuous culture, 12, 50, 97,
56 116, 117, 119, 120, 122,
energy release and 123, 129, 130, 134, 137,
sequestration, 54 138, 140, 142, 143, 160,
oxidative and substrate level 189
phosphorylation, 55–9 continuous filtration, 213
role of adenosine continuous operation, 12, 88, 116,
triphosphate, 54–5 117, 214
Carman-Kozeny equation, 214 continuous plug flow reactor, 88
catabolic pathways, 59–71 continuous process
catabolism, 18, 53, 59, 62 basic model equations
catabolite activator protein, 48 development, 117–27
cell concentration data, 109, 110 cell and substrate concentrations
cell counts, 110 with multiple feed
cell death rate, 132 concentration, 126
cell disintegration, 211, 219 cell and substrate concentrations
cell dry weight, 109, 110, 111 with single feed
cell rupture, 217–19 concentration, 125
cellulases, 29, 30 customised continuous culture
cellulose, 21, 28, 29, 59, 166, 226, configurations, 138–40
231 design equations, 116–40
237

Index
empirical deviations from degree of sterility, 193, 194, 196,

predictions of basic model 202
equations, 127–32 Del Factor, 193
laboratory scale bubble column deoxyribonucleic acid, 36
reactor, 118 desorption, 87
modified model equations diauxie effect, 48
incorporating endogenous dilution rate, 119, 120, 122, 123,
metabolism, 132–58 124, 125, 126, 127, 129,
modified model equations 130, 132, 133, 134, 135,
incorporating energy of 142
maintenance, 135–8 disaccharides, 28
simple continuous culture dispersion model, 201
system incorporating a DNA, 16, 36, 37, 38, 40, 41, 42,
CSTR, 119 43, 44, 45, 46, 49, 109,
wild type selection during 110
culture of genetically doubling time, 107, 108
modified organisms, 129 downstream processing, 209–32
continuous sterilisation, cell rupture and cell extract
199–203 separation, 217–19
continuous stirred tank reactor, cells and extracellular fluid
88, 116 separation, 213–17
CPFR, 88, 91, 92 microbial products recovery,
critical dilution rate, 125, 126, 212
127, 128, 130 potential recovery operations,
cross-linked enzyme aggregates, 87 211–13
CSTR, 88, 89, 91, 92, 116, 117, soluble products concentration
119, 120 and purification, 219–32
cyclic fed-batch, 144
cyclic fed-batch operation, 144 ‘e-fold’ generations, 108
cysteine, 31–2 Eadie–Hofstee relationship, 78,
114, 123
D-stereoisomers, 26 effectiveness factor, 95
Damköhler number, 201 electron transport chain, 56, 57
deacceleration phase, 112 electrophoresis, 211, 220, 232
death phase, 107, 111 endogenous metabolism, 98,
deep bed filtration, 189, 203, 204, 132–5, 137, 139, 142
206 endogenous respiration, 132
degree of sterilisation, 190, 196, endogenous respiration constant,
197, 199, 200, 201, 202 132
238

Index
energy generation, 10, 17, 34, 53, enzyme respression, 47

54–9, 59–71 enzyme retention, 86
energy of maintenance, 98, 135–8, enzyme–substrate complex, 83
142 enzyme–substrate–inhibitor
entrapment, 87 complex, 81, 83
environmental conditions, 221 enzyme synthesis, 44
enzyme activity, 44 enzymes
enzyme decay constant, 85 as biocatalysts, 75–96
enzyme factories, 13 enzyme kinetics with inhibition,
enzyme immobilisation, 87, 88 78–84
enzyme induction, 46 enzyme kinetics with no
enzyme-inhibitor complex, 79, 83 inhibition, 76–8
enzyme kinetics, 76, 78 enzyme reactors with
with inhibition, 78–84 immobilised enzymes,
competitive inhibition 86–95
kinetics, 79–81 enzyme reactors with soluble
mixed inhibition kinetics, enzymes, 84–6
82–4 Equation Solver in Excel, 167
uncompetitive inhibition eubacteria, 9
kinetics, 81–2 eukaryotes, 8, 12–15, 16, 17–18
with no inhibition, 76–8 cellular structure and metabolic
enzyme reactors, 76, 84, 86, 91, reactions sites, 17–18
92 intracellular structures, 16
with immobilised enzymes, microscopic morphology, 12–15
86–95 exponential growth phase, 106,
continuous enzyme processes 107, 109, 110, 111, 112,
with kinetically controlled 113
reaction, 88–92
continuous enzyme processes facultative anaerobes, 59
with transport controlled FAD, 34
reaction, 92–5 fatty acid synthesis, 71–3
CPFR schematic, 90 fatty acids, 20, 30, 31, 63, 68, 70,
CSTR schematic, 89 71, 72
immobilisation techniques, fed-batch bioprocess
86–8 design equations, 140–4
laboratory membrane reactor fed-batch culture, 97, 140, 141,
housing ceramic support for 142, 161, 189
enzyme immobilisation, 88 fed-batch process, 67
with soluble enzymes, 84–6 Fick’s Second Law, 154
239

Index
filter sterilisation, 203–7 continuous sterilisation,

filtration, 109, 189, 203, 204, 213, 199–203
214, 215, 216, 217, 219, dependence of thermal death
225, 227 and degradation rates on
final electron acceptor, 64, 147 temperature, 198
flavin adenine dinucleotide, 34 influence of sterilisation
flocculation, 217 temperature on sterilisation
flow regime, 172, 173, 176, 177, efficiency, 192
179–80, 182, 184–5, 185–7 kinetics, 190–3
fractional precipitation, 221 media and equipment, 190–203
fungi, 12–15 thermal destruction of
contaminating
gassing out procedure, 162, 166, microorganisms, 203
168 hemicellulose, 29
gel chromatography, 231 Henry’s Law, 159
gel filtration, 231 hierachical system, 8
gel regime, 226 high pressure homogenisation,
gene, 8, 44, 45, 46, 47, 48 217–18
generation time, 108, 109 HTST sterilisation, 198, 200
genetic engineering, 49, 50, 76 hydrocarbons, 21
genetic modification, 49–50
genetic regulation, 44–8 impeller tip speed, 178–9
geometric similarity, 172, 173, in situ product removal, 139
175, 177, 181 inducer, 46, 48, 101, 123, 141
geometrical similarity, 173 inertial impaction, 206
gluconeogenesis, 31, 67, 73 insulin, 4–5
glucose isomerase, 75 interfacial area per unit liquid
glycogen, 29, 73 volume, 94
glycolysis, 31, 59–62, 63, 65, 66, interfacial area per unit volume,
72 151, 152, 154, 155, 157
glyoxylate shunt, 67 ionic polymers, 223
GMO, 39, 50, 86, 101, iron, 99
129, 130
Gram negative, 17 ketones, 26, 28
Gram positive, 17 ketoses, 26
gravity sedimentation, 216–17
lac operon, 46, 47
heat sterilisation lacI, 47
batch sterilisation, 193–9 lactose, 28
240

Index
lag phase, 48, 106, 112 Michaelis–Menten equation, 77,

Latin binomial system, 10 78, 80, 81, 84, 85, 94, 95
Le Chatelier’s Principle, 82 Michaelis–Menten kinetics, 93
limiting substrate, 112, 113, 130 microbial kinetics
Lineweaver–Burk relationship, 78, batch, continuous and fed-batch
80, 82, 84, 114, 123 processes, 97–146
lipids, 30–1, 33, 130 batch process design equations,
liquid extraction, 220, 227–9 101–16
log penetration model, 204, 205, continuous process design
206 equations, 116–40
low dilution rate, 130, 131, 134, fed-batch bioprocess design
135, 137, 138, 139 equations, 140–4
LTLT sterilisation, 199 nutrient medium, 98–101
microbiology, 7–23
maintenance coefficient, 136 cellular structure and metabolic
maltose, 28 reactions sites, 15–18
mass transfer limitation, 87, 93, classification according to
95 carbon and energy
Matlab, 168 requirements, 18–20
mechanical rupture, 217 filamentous fungal colonies, 14
media sterilisation, 189, 190 intracellular structures of
membrane separation, 211, 220, prokaryotes and
224–7 eukaryotes, 16
metabolic macromolecules, 25–38 microorganisms, 8–15
carbohydrates, 26–30 nutrient requirements, 21–2
lipids, 30–1 schematic of classification
nucleosides, nucleotides and according to carbon and
nucleic acids, 33–8 energy requirements, 19
proteins, 31–3 the Phylogenetic Tree of Life, 9
metabolic pathways, 8, 25, 26, 30, microorganisms, 8–15
31, 33, 53, 190 microscopic morphology, 11–15
metabolism, 25, 48, 53, 54, 57, eukaryotes, 12–15
62, 63, 66, 99, 132, 133, filamentous fungal colonies,
134, 135, 137, 139, 142, 14
147, 163, 171, 190 prokaryotes, 11–12
methanogens, 20 taxonomy, 8–11
Methanopyrus, 10 mitochondria, 17, 68, 72
Michaelis–Menten constant, 77, mixed inhibition, 79, 82–4
81, 84 mixing, 66, 102, 117, 128, 142,
241

Index
160, 171, 172, 173, 176, nucleic acids, 33, 36–8, 99

177, 178, 180, 181, 182, nucleosides, 33–6
184, 186, 187, 224 nucleotides, 33–6, 37, 38, 40, 42,
mixing time, 176 44, 53, 54, 99
modified gassing out procedure, adenosine mono-, di- and
166 triphosphate, 35
molar flow rate of oxygen nicotinamide adenine
entering, 158 dinucleotide, flavin adenine
molar flow rate of oxygen exiting, dinucleotide and coenzyme
158–9 A, 36
molar flux, 151 parent purine and pyrimidine
molecular biology, 8, 39–51 compounds, 34
enzyme synthesis regulation, RNA and DNA, 37
45 nutrient medium, 21, 22, 97,
genetic modification, 49–50 98–101, 104, 117, 120,
genetic regulation, 44–8 141, 199
protein synthesis, 43
replication, 40–1 obligate aerobes, 58
transcription, 41 operator, 45, 46, 47
translation, 41–4 operon, 45, 46, 47, 48
molecular cloning, 49 OTR, 148, 149, 150, 151, 152,
molecular diffusion, 151 155, 156, 157, 158, 159,
Monod growth kinetics, 11, 13, 160, 161, 162, 164, 166,
108–9, 111, 121 173, 174
Monod Model, 112, 113, 114, OUR, 148, 158, 159, 164, 165,
120, 123, 129, 133, 136, 167
143, 147 overall volumetric mass transfer
monohydroxyaldehydes, 26 coefficient, 94
monohydroxyketones, 26 overall volumetric oxygen transfer
monosaccharides, 26 coefficient, 147–69
morphology, 7, 11, 12, 13, 14, oxidative phosphorylation, 56, 57,
111 58, 59, 62, 65, 147
mRNA, 41, 42, 43, 44, 45, 47, 48 oxygen, 99
oxygen limiting, 58
NAD+, 34 oxygen mass balance, 158
negative modulation, 83 oxygen probe, 161, 162
nicotinamide dinucleotide, 34 oxygen solubility, 147, 148, 150,
nitrogen, 22, 99–100 151, 156, 157, 159, 160,
non-competitive inhibition, 79, 84 161, 163
242

Index
oxygen transfer, 7, 21, 58, 102, palmitic acid, 70

117, 148, 149, 150, 161, Péclet number, 201
168, 171, 172, 174, 176, Penetration Theory, 149
178, 179, 181, 183–4, 185, penicillin amidase, 76
186, 187 peptidoglycan, 15
oxygen transfer coefficient, pharming, 49
152 phospholipids, 30
oxygen transfer limitation, 13, phosphorous, 100
172, 184 photo-autotrophs, 20
oxygen transfer rate, 147–69, 172, Phylogenetic Tree of Life, 9
173 plasmids, 16, 49
design equations, 149–57 polyhydroxyaldehydes, 28
bubble diameter and size polyhydroxyalkonates, 71
distribution in bubble polymerase chain reaction, 49
column reactor, 153 polypeptide, 31, 32, 41, 42, 43,
edge detection on original 44, 45
image and contrast polypeptide chains, 32
mapping of detected polysaccharides, 28
bubbles, 154 positive modulation, 83
possible resistances to oxygen potassium, 22
transfer according to precipitation, 87, 88, 220,
Two Film Theory model, 221–4
150 precise fractionation, 224
measurement, 157–68 pressure step procedure, 166, 167,
quantification under dynamic 168
conditions, 161–8 probe constant, 166, 167
dynamic methodologies prokaryotes, 8, 11–12, 15–17, 45,
assuming a negligible probe 111, 215, 216
response lag, 162–5 cellular structure and metabolic
dynamic methodologies reactions sites, 15–17
incorporating a probe intracellular structures, 16
response lag, 165–8 microscopic morphology, 11–12
oxygen concentration profile promoter, 45, 46, 47, 48
during the dynamic method proteins, 4, 15, 31–3, 38, 47, 99,
in a system with respiring 220, 221, 222, 223, 224,
cells, 163 229, 231, 232
quantification under steady state pseudo steady state, 143, 144
conditions, 158–61 PT, 149
oxygen utilisation rate, 147, 148 purification programme, 33, 209
243

Index
rate of thermal death, 191 slime layers, 16, 128, 215

reaction velocity, 76, 77, 80, 81, solvent extraction, 227–8,
84, 94, 95 229
recombinant DNA, 4, 5, 49 specific growth rate, 108, 109,
regulatory gene, 46 111, 112, 113, 114, 115,
replication, 11, 40–1, 107, 111 120, 122, 123, 126, 127,
repressor, 46, 47, 123 129, 147
repressor molecule, 46 spores, 11, 12, 13, 14
respiratory chain oxidation, 57 sporulation, 12
respiratory quotient, 142 SRT, 149
response lag, 161, 162, 165, 166, starch, 4, 28, 29, 30, 59, 75
167, 168 stationary phase, 107, 110, 111,
reverse osmosis, 225, 226, 227 229, 230
Reynolds number, 177, 179, 180, steady state, 89, 90, 120, 121,
182, 184, 185, 187, 201 123, 124, 125, 126,
ribonucleic acid, 36, 37, 41, 45, 127, 133, 136, 137, 138,
46, 47, 48, 109, 131 140, 143, 144, 152, 153,
ribosomes, 16, 17, 42, 46 154, 158, 159, 160, 161,
RQ, 142 201
rRNA, 42 stirred tank reactor, 102, 105
structural genes, 45, 46, 47, 48
salt precipitation, 222 substrate inhibition, 114
salting out, 222, 223 substrate level phosphorylation,
‘salting out’ constant, 222 55–9, 61, 64, 65, 67
‘salting out’ equation, 222 substrate limitation, 130, 131,
‘salting out’ technique, 222 141
saturation constant, 112 sucrose, 28
Sauter mean diameters, 152 Sulfolobus, 10
scale up criterion, 172, 173, 174, Surface Renewal Theory, 149
178, 179, 180, 181, 182,
183, 184, 185 thermal death, 191, 192, 193, 198,
secondary metabolites, 116, 138, 199, 200
140 thermal death rate constant, 191
sedimentation, 213, 216, 217 thermal degradation, 191, 193,
selective pressure of continuous 198, 199, 200, 201
culture, 130 Thiele modulus, 95
shear stress, 171, 172, 173, 176, transcription, 40, 41, 44, 45, 46,
178, 179, 181, 182, 183, 47, 48
184, 186, 187 translation, 40, 41, 42, 43, 45
244

Index
tricarboxylic acid cycle, 31, 35, ultrasound, 218

62–8, 64, 66, 67, 68, 70, uncompetitive inhibition, 79,
72 81–2, 84
triglycerides, 20
triplet code, 41, 42 wall growth, 128
tRNA, 41, 42, 43
Two Film Theory, 149 xylose isomerase, 4
ultrafiltration, 86, 219, 224, 225, yield coefficient, 115

226 yield constant, 124
245

Index 2013 Bioprocess-Engineering

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Index

absolute filtration, 204 anaerobic fermentation, 58, 59,

Published by Woodhead Publishing Limited, 2013

flask cultures in shaker oxygen transfer, 185–6

Published by Woodhead Publishing Limited, 2013

carbon metabolism, 53–74 centrifugation, 109, 213, 216,

Published by Woodhead Publishing Limited, 2013

empirical deviations from degree of sterility, 193, 194, 196,

Published by Woodhead Publishing Limited, 2013

energy generation, 10, 17, 34, 53, enzyme respression, 47

Published by Woodhead Publishing Limited, 2013

filter sterilisation, 203–7 continuous sterilisation,

Published by Woodhead Publishing Limited, 2013

lag phase, 48, 106, 112 Michaelis–Menten equation, 77,

Published by Woodhead Publishing Limited, 2013

160, 171, 172, 173, 176, nucleic acids, 33, 36–8, 99

Published by Woodhead Publishing Limited, 2013

oxygen transfer, 7, 21, 58, 102, palmitic acid, 70

Published by Woodhead Publishing Limited, 2013

rate of thermal death, 191 slime layers, 16, 128, 215

Published by Woodhead Publishing Limited, 2013

tricarboxylic acid cycle, 31, 35, ultrasound, 218

ultrafiltration, 86, 219, 224, 225, yield coefficient, 115

Published by Woodhead Publishing Limited, 2013

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