Index

A

A (adenine), 45, 47

A. nidulans, 478

Ab (antibody) macromodule, 34

Acetone production, 584586

Acid formers, in waste treatment, 564

Acidophiles, 14

Actin filaments, 25, 433

Actinomycetes, 19

Activated-sludge processes, biological waste treatment, 551553

Active cell immobilization, 298302

Active sites, 63

Acylation, 115

ADC (adsorption chromatography), 410411

ADC (antibody-drug conjugate), 36

Adenosine monophosphate (AMP), 45

Adenosine triphosphate (ATP). See ATP (adenosine triphosphate).

Adsorbent-added activated-sludge process, 557558

Adsorption

ADC (adsorption chromatography), 410411

cells, 300301

enzyme immobilization, 87

Freundlich adsorption isotherm, 403404

immobilized cell systems, 300301

separation of soluble products, 403409

Adsorption chromatography (ADC), 410411

Adsorption zone, separation of soluble products, 405

Aeration, bioreactor scale-up, 331337

Aerobic bioprocesses. See also Anaerobic bioprocesses.

baker’s yeast production, 588590

citric acid production, 586588

HFCS (high-fructose corn syrup) production, 593595

penicillin production, 590592

VEFCS (very enriched fructose corn syrup) production, 595

Aerobic organisms, 14

Aerobic respiration, glycolysis, 149

Aerotaxis, 138

AFC (affinity chromatography), 411, 414419

Ag (antigen) macromodule, 34, 36

Aggregates in plant cell cultivation, 460

Agitation, bioreactor scale-up, 331337

Agricultural wastes, biological waste treatment, 549

Airlift system, bioreactor scale-up, 329330

Ajmalicine from periwinkle, 465

Aldehydes, 38

Algae

Chlorella, 27

definition, 27

Dunaliella, 27

microscopic eucaryotes, 27

Scenedesmus, 27

size, 27

Spirulina, 27

Alkaliphiles, 14

Alkylation, 116

Allosteric enzymes, 7173

Allostery, 7173

Ameboid motion, 27

Amensalism, model of mixed culture interaction, 538539

Amino acids. See also Proteins.

in cell construction. See Cell construction, amino acids.

chemical structure, 31

a dipolar molecule, 32

isoelectric point, 32

natural, 31

peptide bond, 32

in polypeptides, 31

proteinogenic, 31

pyrrolysine, 31

selenosysteine, 31

zwitterion, 32

Aminoacyl site, 125

Aminoacyl-tRNA synthetases, 125

Amoebae, 27

AMP (adenosine monophosphate), 45

Amplifying DNA, 260. See also PCR (polymerase chain reaction).

Amylases, 101

Amylopectin, 41

Amylose, 41

Anabolism, definition, 146

Anaerobic bioprocesses. See also Aerobic bioprocesses.

acetone production, 584586

butanol production, 584586

ethanol production, 578581

lactic acid production, 581584

Anaerobic digestion, biological waste treatment, 564566

Anaerobic metabolism

anaerobic respiration, 161

denitrification, 161

ED (Entner–Doudoroff) pathway, 161

fermentation, 161

overview, 161163

Anaerobic organisms, 14

Anaerobic respiration, 149, 161

Anchorage-dependent cells, 432, 435

Animal cell cultivation

anchorage-dependent cells, 435

basic techniques, 434437

cancer linkage to cell transformation, 435

contact inhibition, 435

continuous cells, 435

growth dynamics, 441443

growth media, 437441

hybridoma cells, 436

immortal cells, 435

insect cells, 435436

mammalian cell culture, 436437

mortal cells, 435

nonanchorage-dependent cells, 435

primary culture, 434435

products of, 447448

secondary culture, 435

senescence, 435

transformed cells, 435436

Animal cell cultivation, bioreactor considerations

constraints, 443

entrapped cells in stirred reactors, 445447

hollow-fiber reactors, 445

nonstirred reactor systems, 444445

single-use disposable systems, 445, 447

stirred-tank bioreactors, 447

suspended cultures, 447

Animal cells

actin filaments, 433

anchorage-dependent cells, 432

biochemistry, 431434

centrosome, 433

cilia, 433

cisternae, 433

cytoskeleton, 433

cytosol phase cytoplasm, 432

dictyosome, 433

ER (endoplasmic reticulum), 432

glyoxysomes, 433

Golgi body, 433

intermediate filaments, 433

lumenal phase cytoplasm, 432

lysosomes, 432

metabolism of nutrients, 433434

microtubules, 433

microvilli, 432

mitochondria, 432

nucleoli, 433

perinuclear space, 433

peroxisomes, 433

size, 431

structure, 431434

types of filaments, 433

Animal vs. plant eucaryotes, 22

Anisotropic membranes, separation of soluble products, 395

Anoxygenic photosynthetic bacteria

bacteriochlorophyll, 19

light-gathering pigments, 19

in photosynthesis, 19

Antibodies, proteins. See Proteins, antibodies.

Antibody (Ab) macromodule, 34

Antibody–antigen complex, 36

Antibody–antigen interaction, 36

Antibody–drug conjugate (ADC), 36

Anticancer agent (Taxol), in plant cell cultivation, 456457

Anticodons, 125

Antigen (Ag) macromodule, 34, 36

Apoenzyme, 61

Apparent growth yield, 179180

Aqueous two-phase affinity partition extraction, separation of soluble products, 389

Aqueous two-phase extraction, separation of soluble products, 389390

Archaebacteria

procaryotes, 15

structure of, 20

Artificial tissue/organs, 520521

Ascospores, 25

Asexual reproduction

eucaryotes, 23

microscopic eucaryotes, 25

Asparaginase, uses for, 102

ATP (adenosine triphosphate)

maintenance coefficient, 227229

oxygen consumption, 227229

phosphate bonds, 45

regularities, 229

ATP (adenosine triphosphate), yield coefficients

maintenance, 227229

oxygen, 227229

theoretical predictions, 235236

Autographa californica (baculovirus), 265, 480

Autologous implantation, 523

Autotrophic metabolism, 163165

Autotrophs, 52

Auxotrophic mutants, 250251

B

B. subtilis

description, 19

genetic engineering, host-vector systems, 477

Bacillus (cylindrical) cells, 14

Bacillus (rod) cells, 14

Back mutations, 248249

Bacteria. See also Archaebacteria; Eubacteria (true bacteria).

architecture of, 21

capsule, 20

chromatophores, 20

endospores, 20

Gram staining, 18

intracellular spores, 20

outside cell wall. See Capsule.

photosynthesis, 20

Bacterial microcompartments (BMCs), 20

Bacteriochlorophyll, 19

Bacteriophages. See Phages.

Baculovirus (Autographa californica), 265, 480

Baker’s yeast production, 588590

Balanced growth, 177

Balanced growth assumption, 192

Bardenpho process, biological waste treatment, 571

Basal level of proteins, 131

Basic local alignment search tool (BLAST), 271

Batch bioreactors

vs. continuous, 276278

genetic instability, 277

market economics, 277

operability, 277

semicontinuous. See Fed-batch bioreactors.

variable-volume continuous culture. See Fed-batch bioreactors.

Batch bioreactors, modifying

chemostat with recycle, 278281

external membrane bioreactors, 295

fed-batch operation, 288293

internal membrane bioreactors, 295

membrane bioreactors, 294297

multistage chemostat systems, 281287

perfusion systems, 293294

Batch cell growth, growth patterns

apparent growth yield, 179180

balanced growth, 177

death phase, 179

deceleration phase, 178

decline phase, 179

diauxic growth, 177

endogenous metabolism, 178

exponential phase, 177

growth-associated products, 183

lag phase, 175177

Luedeking–Piret equation, 183

maintenance, 180

maintenance energy, 178

microbial products, classifying, 183184

mixed-growth-associated product formation, 183

nongrowth-associated product formation, 183

nongrowth-related functions, 181182

phases, 175

primary metabolites, 178

secondary metabolites, 178

stationary phase, 178179

yield factors for aerobic growth, 182

Batch cell growth, quantifying

cell concentration, quantifying, 170

cell mass concentration, determining, 171175

cell number density, determining, 171

counting viable cells, 171

direct cell counting, 171

direct methods, 172

dry weight, determining, 171172

hemocytometer, 171

indirect methods, 172175

optical density, 172

packed cell volume, 172

particle counters, 171

Petroff–Hausser counting chamber, 171

plate counts, 171

turbidity, 172

viable count, 171

Batch cell growth kinetics

critical oxygen concentration, 187188

DO (dissolved oxygen) effects, 187188

environmental conditions, effects of, 184189

heat generated by microbial growth, 190191

OTR (oxygen transfer rate), 188

OUR (oxygen uptake rate), 188

pH effects, 186

redox potential, 189

temperature effects, 184185

Batch cell growth kinetics, quantifying

balanced growth assumption, 192

batch growth, 200201

Blackman equation, 194

carrying capacity, 197198

cell structure, 191

chemically structured models, 202207

Contois equation, 194

cybernetic models, 207208

extrinsic concentration, 202

Gompertz equation, 200201

half-velocity constant, 192193

intrinsic concentration, 202

logistic equations, 197200

maximum growth potential, 200201

models for filamentous organisms (molds), 201

models for transient behavior, 201202

models with growth inhibitors, 195197

models with time delays, 202

Monod equation, 192194, 197

Moser equation, 194

overview, 191192

product formation, 200201

product inhibition, 196

saturation constant, 192193

segregation, 191

structured models, 191

substrate inhibition, 195

substrate-limited growth, 192194

Tessier equation, 194

unbalanced growth, 191

unstructured nonsegregated models, 192201

Batch growth, 200201

Batch kinetics, 6970

Bed depth–service time equation, separation of soluble products, 405409

Bidirectional DNA, 117

Binding, immobilized cell systems, 300302

Biochemical engineering

vs. bioprocess engineering, 3

bioreaction engineering, 2

bioseparations, 2

definition, 2

Biochemistry of animal cells, 431434

Biodegradation of xenobiotics (toxic aromatic compounds), 157158

Bioelectricity from wastes, 598600

Bioenergetics, 146148

Bioengineering, definition, 2

Bioengineers, definition, 2

Biofuel and bioenergy production

bioelectricity from wastes, 598600

gaseous fuels from biomass, 597598

hydrogen gas production, 597598

liquid fuel production, 596597

methane production, 597598

MFCs (microbial fuel cells), 598600

Bioinformatics, 271

Biolistic processes, 265266

Biological engineering, definition, 2

Biological films, 303304

Biological oxygen demand (BOD), 550

Biological waste treatment. See Mixed culture, biological waste treatment.

Biologists

research approaches, 3

working with engineers, 49

Biomedical engineering, definition, 2

Biomolecular engineering, definition, 2

Biopharmaceutical products from genetic engineering, 473

Bioprocess engineering

vs. biochemical engineering, 3

industrial uses for. See Aerobic bioprocesses; Anaerobic bioprocesses; Biofuel and bioenergy production.

origins of, 8

Bioprocess engineering, medical uses for

artificial tissue/organs, 520521

autologous implantation, 523

bioreactor considerations. See Bioreactors, bioprocess engineering.

cartilage replacement, 522523

chondrocyte culture, 522523

endocytosis, 525

endosomes, 525

gene therapy using viral vectors, 523528

mass production of retrovirus, 527528

models of viral infection, 524527

regenerative medicine, 519523

skin replacement, 521522

tissue engineering, 519523

viral gene delivery systems, 524

Bioprocesses, regulatory constraints, 910

Bioreaction engineering, 2

Bioreactor considerations, animal cell cultivation

constraints, 443

entrapped cells in stirred reactors, 445447

hollow-fiber reactors, 445

nonstirred reactor systems, 444445

single-use disposable systems, 445, 447

stirred-tank bioreactors, 447

suspended cultures, 447

Bioreactor considerations, plant cell cultivation

ajmalicine from periwinkle, 465

cell immobilization, 463465

hairy roots, 466467

mixotrophic cultures, 467

organized tissues, 466467

photoperiod control, 467

root mats, 467

submerged culture, 467

suspension cultures, 462463

Bioreactor instrumentation and control

of chemical environment, 350351

control strategies, 355

data logging, 354

exit-gas measurement, 352

FTIR (Fourier transform infrared), 352

gateway sensors, 354

HPLC (high-pressure liquid chromatography), 352

insertable probes, 349351

measuring active fermentation, 349352

of physical environment, 350

probe drift, 351

probe fouling, 351

recalibrating probes in situ, 351

using information from, 352355

Bioreactor scale-up

bioreactors, definition, 324

common approaches, 337342

fermenters, definition, 324

geometric similarity, 337

internal mechanical agitation, 324329

overview of reactor types, 324

practical limits, 341

Rushton impeller, 325

Bioreactor scale-up, common difficulties

aeration, 331337

agitation, 331337

airlift system, 329330

bubble column reactors, 329330

cleaning, 329

dynamic method for oxygen removal, 335

energy efficiency, 329

foaming, 328

heat transfer, 331337

internal mechanical agitation, 324329

loop reactors, 329330

oxygen solubility, 332335

single-use bioreactors, 330331

steady-state method for oxygen removal, 334

sterility, 329

unsteady-state method for oxygen removal, 333

working volume, 328

Bioreactors. See also Batch bioreactors; Continuous bioreactors.

attached cells, 311313

cleaning, 329. See also Sterilizing process fluids.

cultivation method, choosing, 276278

definition, 324

hybrids, 311313

immobilized cell systems, 309311

impellers, 324325

microreactors, 342348

mixed and forcefully aerated, 314

overview of reactor types, 324

packed-bed, 314

rotating drum, 314

scaling down, 342348

for solid-state fermentation, 313316

spargers, 324

sterilizing. See Sterilizing process fluids.

suspended cells, 311313

tray, 314

Bioreactors, medical applications

body-on-a-chip systems, 530531

extracorporeal artificial liver, 530

flatbed reactors, 530

fluidized bed reactors, 530

hematopoiesis, 529530

iPS (induced pluripotent stem) cells, 529

membrane-based units, 530

microphysiological systems, 531

multiorgan-on-a-chip systems, 531

PBPK (physiologically based pharmacokinetic) model of the human body, 531

pluripotent stem cells, 529

progenitor cells, 529

stem cells, 529530

Bioseparations, 2

Biosynthesis, 158161

gluconeogenesis, 160

HMP (hexose monophosphate) pathway, 158161

overview, 158161

pentose–phosphate, 158161

Biotechnology, definition, 2

Blackman equation, 194

BLAST (basic local alignment search tool), 271

Blue-green algae (cyanobacteria)

growth environment, 14

photosynthesis, 19

BMCs (bacterial microcompartments), 20

BOD (biological oxygen demand), 550

Body-on-a-chip systems, 530531

Bottle plant, penicillin production, 6

Briggs, G. E., 66

Bubble column reactors, scaling up, 329330

Butanol production, 584586

C

C (cytosine), 45, 47

Cabbage looper (Tricoplusia ni), 480

Cake resistance, separation of insoluble products, 376378

Callus cultures in plant cell cultivation, 458459

Calvin cycle, 163165

Campylobacter jejuni bacterium, 129

Cancer

bioprocesses for the anticancer agent Taxol, 456457

linkage to cell transformation, 435

transformed cells, 479

Capsid coating, viruses, 17

Capsule, bacteria, 20

Carbohydrates

amylopectin, 41

amylose, 41

in cell construction, 3742

cellulose, 41

deoxyribose, 39

disaccharides, 40

D-ribose, 39

glycans, 42

glycogen, 41

glycosylation, 42

lactose, 40

monosaccharides, 3739

photosynthesis, 37

polysaccharides, 4042

role in cells, 37

sucrose, 40

Carbon compounds, macronutrients, 5253

Carrying capacity, 197198

Cartilage replacement, 522523

Catabolism

definition, 146

of glucose, 149152

Catabolite repression, 131

Catalytic proteins, 30

cDNA (complementary DNA), 260

CDRs (complementarity determining regions), 36

Cell adsorption, 300301

Cell concentration, quantifying, 170

Cell construction

carbohydrates, 3742

composition of living cells, 28

fats, 4245

fatty acids, 4245

integral member proteins, 43

lipids, 4245

nucleic acids, 4451. See also DNA (deoxyribonucleic acid); RNA (ribonucleic acid).

peripheral member proteins, 43

PHA (polyhydroxyalkanoates), 44

PHB (polyhydroxybutyrate), 44

phosphoglycerides, 43

phospholipids, 43

scientific domain. See Systems biology.

Cell construction, amino acids. See also Proteins.

chemical structure, 31

a dipolar molecule, 32

isoelectric point, 32

peptide bond, 32

in polypeptides, 31

proteinogenic, 31

pyrrolysine, 31

selenosysteine, 31

zwitterion, 32

Cell death

batch cell growth, 179

kinetics of, 356357

in sterilization, 356357

and thermodynamic equilibrium, 51

Cell disruption, separation of insoluble products

mechanical, 383385

nonmechanical, 384385

Cell division among eucaryotes, 23, 26

Cell growth

culturing cells in a vessel. See Batch cell growth.

growth factors, 139

growth media, 5556

net specific growth rate, 169170

rate of microbial growth, 169170

Cell growth in continuous culture

cultivation devices, 208210

overview, 208

PFRs (plug flow reactors), 208, 210

turbidostats, 208210

Cell growth in continuous culture, chemostats

CFSTR (continuous-flow, stirred-tank reactor), 210

description, 208210

deviations from ideality, 218

ideal device, 210217

maintenance coefficient, 213

mutations, 217

as a tool, 217218

washing out a culture, 211

Cell immobilization, 463465

Cell lysis, 18

Cell mass concentration, determining, 171175

Cell motion, eucaryotes, 2425

Cell nomenclature

archaebacteria, 15

by cell structure, 15. See also Eucaryotes; Procaryotes.

definition, 15

dual names, 15

eubacteria (true bacteria), 15

genes of a whole organism. See Genome.

genus, 15

Latin names, 15

for microorganisms, 15

for organizing knowledge. See Cell taxonomy.

within procaryotes, 15

recognized subdivisions of organisms, 16

viruses, 15

Cell number density, determining, 171

Cell nutrients

categories of, 51. See also Macronutrients; Micronutrients.

growth media, 5556

intracellular composition of cells, 5152

overview, 5152

thermodynamic equilibrium and death, 51

Cell receptors, role of, 137139

Cell separation. See Separation.

Cell shapes

cylindrical (bacillus), 14

rod (bacillus), 14

spherical, elliptical (coccus), 14

spiral (spirillum), 14

Cell taxonomy

definition, 1415

for naming organisms. See Cell nomenclature.

for organizing knowledge, 1415

Cell-free protein synthesis (CFPS), 484

Cells. See also DNA (deoxyribonucleic acid); RNA (ribonucleic acid).

active transport, 135137

acylation, 115

aerotaxis, 138

alkylation, 116

cell receptors, role of, 137139

cellular differentiation, 137139

central dogma, 114117

chemotaxis, 138

codons. See Genetic code.

cotranslational modifications, 115116

disulfide bond formation, 115

energy-independent uptake, 135137

estimation of elemental composition, 236237

facilitated diffusion, 135137

genes, 116117. See also Genetic code.

genetic code. See Genetic code.

glycosylation, 115

group translocation, 135137

hormones, 139

hydroxylation, 116

inteins, 116

introns, 116

lipidation, 116

macromolecules. See DNA (deoxyribonucleic acid); Protein; RNA (ribonucleic acid).

major groups of. See Eucaryotic cells; Procaryotes.

metabolic regulation. See Metabolic regulation.

metabolism, 137139

mRNA splicing, 116

with or without oxygen. See Facultative organisms.

oxygen toxicity. See Anaerobic organisms.

passive diffusion, 135137

phosphorylation, 116

phosphotransferase system, 137

phototaxis, 138

posttranslational modification, 115116

protein splicing, 116

proton-motive forces, 136137

replication, 114

retrotransposons, 115

reverse transcriptase, 115

reverse transcription, 115

sensing external environment, 135139

steroid hormone receptors, 139

sulfation, 116

telomere synthesis, 115

transcription to RNA. See DNA transcription.

transfer of biological information, 114117

translation into proteins, 114, 127129

transporting small molecules across membranes, 135137

ubiquitination, 116

ubiquitins, 116

using oxygen. See Aerobic organisms.

Cells and their environments

acidophiles, 14

aerobic organisms, 14

alkaliphiles, 14

anaerobic organisms, 14

cyanobacteria, 14

extreme. See Extremophiles.

extremophiles, 1314, 21

facultative organisms, 14

halophiles, 14, 21

high salt concentrations. See Halophiles.

high temperatures. See Thermophiles.

low temperatures. See Psychrophiles.

mesophiles, 14

with minimal nutrients. See Cyanobacteria.

moderate temperatures. See Mesophiles.

neutrophiles, 14

oxygen adaptive. See Facultative organisms.

oxygen inhibited. See Anaerobic organisms.

oxygen required. See Aerobic organisms.

pH values 1 or 2. See Acidophiles.

pH values 6 to 8. See Neutrophiles.

pH values above 9. See Alkaliphiles.

psychrophiles, 14

thermoacidophiles, 21

thermophiles, 14

Cell-surface display, 265

Cellular differentiation, 137139

Cellulases, 101

Cellulose, 41

Centrifugal Podbielniak extractors, separation of soluble products, 387388

Centrifugation, separation of insoluble products, 378382

Centrifugation coefficient, separation of insoluble products, 381

Centrosome, 433

Cer locus, 493

CFPS (cell-free protein synthesis), 484

CFSTR (continuous-flow, stirred-tank reactor), 210, 552

Chain, Ernst, 4

Chaperones, 125

Chelating agents, 55

Chemautotrophs, 52

Chemical agents for causing mutations, 250

Chemical environment, monitoring, 350351

Chemical gene synthesis, 259

Chemical oxygen demand (COD), biological waste treatment, 550

Chemical synthesis, penicillin production, 5

Chemical waste treatment, 549

Chemically structured models, 202207

Chemostat with recycle bioreactor, 278281

Chemostats

CFSTR (continuous-flow, stirred-tank reactor), 210

description, 208210

deviations from ideality, 218

ideal device, 210217

maintenance coefficient, 213

mutations, 217

as a tool, 217218

washing out a culture, 211

Chemotaxis, 138

Chlorella algae, 27

Chloroplast, 165

Chloroplasts, 24

CHO (Chinese hamster ovary) cells, 479480, 484485

Chondrocyte culture, 522523

Chromatography. See Separation of soluble products, chromatography.

Chromatophores, 20

Chromosomes, 22

Cilia, 25, 27, 433

Ciliated organisms

definition, 25

vs. flagellated organisms, 25

Ciliates, 25, 27

CIP (clean-in-place) technology, 329

Cisternae, 433

Citric acid cycle, 149

Citric acid production, 586588

Cleaning bioreactors, 329. See also Sterilizing process fluids.

Cloning

alternative strategies, 262263

amplifying DNA, 260

cDNA (complementary DNA), 260

cell-surface display, 265

chemical gene synthesis, 259

codon harmonization, 259

codon optimization, 259

DNA microarray technology, 259

electrophoresis, 263264

expressed DNA, 262

expression of cloned genes, 263265

Gateway cloning, 262

gene bank, 264265

gene library, 264265

Gibson assembly, 262

Golden Gate cloning, 263

GreenGate cloning, 263

hybridization, 259

immunoblot testing, 264

inserting genes into DNA, 260262

introns, 259

isothermal cloning, 262

LIC (ligation independent cloning), 263

ligands, 265

MoClo (molecular cloning), 263

obtaining the gene of interest, 259260

overview, 258

PCR (polymerase chain reaction), 260

phage display, 265

plasmid vectors, 260

probes, 259

recombinant DNA techniques, 258

restriction endonuclease, 262263

restriction enzymes, 259260

reverse transcriptase, 260

shotgun cloning, 259, 264

synonymous mutations, 259

TA cloning, 262

testing for proteins, 264

TOPO cloning, 262

type IIS enzyme, 262263

Western blot testing, 264

yeast-mediated cloning, 263

Clustered regularly interspaced short palindromic repeat (CRISPR), 267, 480

Coagulation, separation of insoluble products, 382

Coccus (elliptical) cells, 14

Coccus (spherical) cells, 14

COD (chemical oxygen demand), biological waste treatment, 550

Coding DNA, 49

Coding RNA, 48

Codon harmonization, 259

Codon optimization, 259

Codons, 116117, 123

Commensalism, model of mixed culture interaction, 538

Commonly added micronutrients, 54

Competent DNA strains, 254

Competition, 536

Competitive inhibitors, enzyme kinetics, 7374

Complementarity determining regions (CDRs), 36

Complementary DNA (cDNA), 260

Complex glycoforms, 129

Concentration, separation of soluble products, 403

Concentration polarization, separation of soluble products, 394395

Concerted feedback inhibition, 134

Conditional mutants, 251

Conidia, 25

Conjugation, 256257

Constitutive exocytosis pathway, 127

Constitutive genes, 132

Contact inhibition, 435

Contact stabilization, biological waste treatment, 557

Continuous bioreactors

vs. batch, 276278

CFSTR (continuous-flow, stirred-tank reactor), 276278

Continuous bioreactors, modifying

chemostat with recycle, 278281

external membrane bioreactors, 295

internal membrane bioreactors, 295

membrane bioreactors, 293294

multistage chemostat systems, 281287

perfusion systems, 293294

Continuous cells, 435, 479

Continuous sterilization, 361

Continuous-flow, stirred-tank reactor (CFSTR), 210, 552

Contois equation, 194

Control sites in aerobic glucose metabolism, 154155

Cooperative binding, 7173

Cooperative feedback inhibition, 134

Core enzymes, 119

Cost of sequencing a complete genome, 270

Cotranslational modifications, 115116

Cotranslational protein translation, 125

Counting viable cells, 171

Covalent binding, 301302

Covalent bonding, 8789

Crabtree effect, 146, 589

CRISPR (clustered regularly interspaced short palindromic repeat), 267, 480

Cristae, 23

Cross-flow filtration, separation of soluble products, 398403

Cross-flow ultrafiltration, separation of soluble products, 398403

Crystallization, purification process, 422423

Cultivation devices, 208210

Cumulative feedback inhibition, 134

Cyanobacteria (blue-green algae)

growth environment, 14

photosynthesis, 19

Cybernetic models, 207208

Cylindrical (bacillus) cells, 14

Cytokinesis, 23

Cytoplasmic membrane, 18, 22

Cytosine (C), 45, 47

Cytoskeleton

animal cells, 433

eucaryotic cells, 25

Cytosol phase cytoplasm, 432

D

Dalton, 36

Damkohler number, 91

Dark phase of photosynthesis, 164

Data logging, 354

Death. See Cell death.

Deceleration phase, 178

Decline phase, 179

Degenerate code, 123

Deletion mutations, 248

Denatured enzymes, 71

Denitrification, 161

Deoxyribonucleic acid (DNA). See DNA (deoxyribonucleic acid).

Deoxyribonucleotides, structure of, 46

Deoxyribose, 39

Depth filters, 362363

Diafiltration, separation of soluble products, 403

Dialysis, separation of soluble products, 392393

Dialysis equilibrium, separation of soluble products, 393

Diauxic growth, 132, 177

Dictyosome, 433

Differentiated tissue in plant cell cultivation, 459

Dimers, 487

Diploid cells, 23

Direct cell counting, 171

Direct methods for counting viable cells, 172

Direct selection mutation, 250

Directed evolution, 512

Disaccharides, 40

Disinfection vs. sterilization, 356

Displacement chromatography, 409

Disposable bioreactors. See Single-use bioreactors.

Dissociation extraction, separation of soluble products, 387388

Dissolved oxygen (DO) effects in batch cell growth kinetics, 187188

Disulfide bond formation, 115

DNA (deoxyribonucleic acid). See also Cells; Nucleic acids; RNA (ribonucleic acid).

amplifying, 260. See also PCR (polymerase chain reaction).

building blocks of. See Nucleotides.

coding sequences, 49

competent strains, 254

DNA methylases, 116

donor, 253

double helix, 48

forming RNA molecules. See DNA transcription.

inserting genes into, 260262

junk DNA. See Noncoding DNA.

major functions of, 48

methylation variation, 116

noncoding DNA, 49

plasmids, 48

proofreading, 118

structure of, 47

Taq (Thermus aquaticus), 14

DNA gyrase enzyme, 117

DNA ligase enzyme, 118

DNA microarray technology, 259

DNA replication

definition, 4748

semiconservative replication, 4849, 117

DNA replication in E. coli. See also E. coli.

bidirectional DNA, 117

DNA gyrase enzyme, 117

DNA ligase enzyme, 118

lagging strands, 118

leading strands, 118

Okazaki fragments, 118

origin of replication, 117

process summary, 118119

proofreading the DNA, 118

replication forks, 117

RNA primer, 117118

unwinding enzymes, 117

DNA shuffling, 512513

DNA transcription

core enzymes, 119

definition, 48

holoenzymes, 119

introns, 121122

mRNA, 121

mRNA splicing, 122

nonsense DNA, 122

polyadenylation, 122

polygenic messages, 121

primary products of, 119

procaryotic vs. eucaryotic cells, 121122

promoter region, 121

reading through a terminator, 121

reverse transcription, 115

rho protein, 121

RNA polymerase enzyme, 119

rRNA, 121

separate protein for each gene, 121

sigma factor, 119

stable RNA species, 121

stop signals, 121

strong promoter, 121

strong terminators, 121

transcription terminators, 121

tRNA, 121

unstable RNA species, 121

weak terminators, 121

DNA translation

aminoacyl site, 125

aminoacyl-tRNA synthetases, 125

anticodons, 125

chaperones, 125

cotranslational protein translation, 125

definition, 48, 123

elongation step, 124125

genetic code, 123124

initiation complex, 125

initiation factors, 125

initiation step, 124125

nonsense codons, 125

peptides from RNA, 48

peptidyl site, 125

posttranslation movement across membranes, 125

posttranslational processing, 125129. See also Eucaryotic cells, posttranslational protein release; Procaryotic cells, posttranslational protein release.

primary steps, 124125

process description, 124125

proteins from RNA, 48

RF (release factor), 125

signal peptides, 125

stop codons, 125

termination step, 124125

DO (dissolved oxygen) effects in batch cell growth kinetics, 187188

Domestic wastes, biological waste treatment, 549

Donnan equilibrium, separation of soluble products, 393

Donor DNA, 253

Double helix, 48

Double-reciprocal plot, 68

D-ribose, 39

Dry weight of cells, determining, 171172

Drying, purification process, 423424

Dunaliella algae, 27

Dynamic method for oxygen removal, 335

Dyno-Mill homogenizer, separation of insoluble products, 384

E

E. coli

cell lysis, 18

cells breaking open. See Cell lysis.

conversion of aspartic acid to aspartyl phosphate, 140142

cytoplasmic membrane, 18

description, 18

DNA replication. See DNA replication in E. coli.

genetic engineering, host-vector systems, 475477, 484485

inner membrane, 18

LPS (Lipopolysaccharide), 18

LPS removal, 18

outer membrane, 18

peptidoglycan, 18

periplasmic space, 18

strong promoters, 491

Eadie–Hofstee plot, 6869

ED (electrodialysis), separation of soluble products, 421422

ED (Entner–Doudoroff) pathway, 161

Effectiveness factor, enzyme immobilization, 9596

Egg cells, 23

Elder, A. L., 5

Electron transport chain, 149, 152154

Electrophoresis

expression of cloned genes, 263264

separation of soluble products, 419420

two-dimensional gel electrophoresis, 270

Electroporation, 265

Electrostatic effects on enzyme immobilization, 98

Elicitors in plant cell cultivation, 460461

Elliptical (coccus) cells, 14

Elongation step, 124125

Elution chromatography, 409

EMP (Embden–Meyerhof–Parnas) pathway, 149152

Encapsulation, cell entrapment, 300

Endocytosis, 525

Endogenous metabolism, 178

Endoplasmic reticulum (ER), 2324, 432

Endosomes, 525

Endospores, 20

Endotoxins. See LPS (Lipopolysaccharide).

End-product inhibition, 133

Energy efficiency, bioreactors, 329

Energy-independent uptake, 135137

Engineered antibodies, 36

Engineers

research approaches, 3

working with biologists, 49

Enhancer regions, 131

Entner–Doudoroff (ED) pathway, 161

Entrapment, 8587

Entrapment, active cell immobilization, 298300, 302

Entrapped cells in stirred reactors, 445447

Environmental conditions, batch cell growth kinetics, 184189

Enzyme activation, 80

Enzyme immobilization

electrostatic effects, 98

steric effects, 98

Enzyme immobilization, diffusional limitations

Damkohler number, 91

effectiveness factor, 9596

on enzymes immobilized in a porous matrix, 9397

on reaction rate, 93

on surface-bound enzymes, 9193

Enzyme immobilization, methods of

adsorption, 87

covalent bonding, 8789

diffusion limitations, 87

entrapment, 8587

enzyme leakage, 87

microencapsulation, 87

surface, 8790

Enzyme induction, 131

Enzyme kinetics. See also Michaelis–Menten kinetics.

allosteric enzymes, 7173

allostery, 7173

cooperative binding, 7173

enzyme activation, 80

insoluble substrates, 8384

Langmuir–Hinshelwood kinetics, 63

mathematical model of, 6365

multiphase enzymatic reactions, 8485

partition coefficient, 85

pH effects, 8082

RST (rate of substrate transfer), 85

saturation kinetics, 6365. See also Michaelis–Menten kinetics.

temperature activation, 8283

temperature inactivation, 83

thermal denaturation, 83

Enzyme kinetics, inhibited

competitive inhibitors, 7374

inhibitors, 73

irreversible inhibitors, 73

mixed inhibition, 76

noncompetitive inhibitors, 73, 7475

reversible inhibitors, 73

substrate inhibition, 7679

uncompetitive inhibitors, 7576

Enzyme kinetics, mechanistic models

quasi-steady-state assumption, 6667

rapid-equilibrium assumption, 6566

Enzyme leakage, 87

Enzymes. See also specific enzymes.

active sites, 30, 35, 63

apoenzyme, 61

classification, 62

containing protein groups, 61

denatured, 71

enzyme-substrate interaction, 63

function of, 6263

holoenzymes, 61

induced fit model, 63

industrial uses for, 100103

integral membrane proteins, 30

isozymes, 61

large-scale production, 9899

lock-and-key model, 63

medical uses for, 100103

naming, 61

orientation effect, 63

proximity effect, 63

regulatory, 30

specific activity, 7071

structure of, 61

units, 70

Enzyme-substrate interaction, 63

Episomes, gene transfer and rearrangement, 256257

Epitopes, 36

ER (endoplasmic reticulum), 432

Eroshin, V. K., 229

Error-prone PCR, 512

Ethanol production, 578581

Eubacteria (true bacteria)

evolution of, 15

Gram staining, 18

photosynthesis, 19

Eucaryotes. See also Procaryotes.

cell division, 23, 26

cell motion, 2425

definition, 15, 22

Eucaryotes, cell structure

actin filaments, 25

animal vs. plant, 22

asexual reproduction, 23

chloroplasts, 24

chromosomes, 22

cilia, 25

ciliates, 25

cristae, 23

cytokinesis, 23

cytoplasmic membrane, 22

cytoskeleton, 25

diploid cells, 23

egg and sperm cells, 23

endoplasmic reticulum, 2324

flagella, 2425

gametes, 23

glycans, 24

glycosylation, 24

glyoxysomes, 24

Golgi bodies, 24

haploid cells, 23

histones, 22

inner membranes, 23

intermediate filaments, 25

interphase, 23

lysosomes, 24

microtubule, 25

mitochondria, 2324

mitosis, 23

nucleus, 22

peroxisomes, 24

photosynthesis, 24

vs. procaryotes, 22

sexual reproduction, 23

size, 22

sterols, 22

thylakoids, 24

tubulin, 25

vacuoles, 24

zygotes, 23

Eucaryotes, microscopic

algae, 27

ascospores, 25

asexual reproduction, 25

fission reproduction, 25

fungi, 25

molds, 2527

protozoa, 2728

yeasts, 25

Eucaryotic cells

in genetic engineering, host-vector systems, 477479

vs. procaryotic cells, DNA transcription, 121122

Eucaryotic cells, posttranslational protein release

Campylobacter jejuni bacterium, 129

complex glycoforms, 129

constitutive exocytosis pathway, 127

exocytosis, 127

glycans, 127

glycoforms, 127129

glycosylation, 127

Golgi apparatus, 127

Golgi trans face, 127

hybrid glycoforms, 129

N-linked glycosylation, 129

OST (oligosaccharyltransferase), 129

protein release, 127

PTMs (posttranslational modifications), 127

regulated exocytosis pathway, 127

simple glycoforms, 129

transport vesicle fusion, 127

Exit-gas measurement, 352

Exocytosis, 127

Exponential growth phase, 177

Expressed DNA, 262

Expression of cloned genes, 263265

External membrane bioreactors, 295

Extracorporeal artificial liver, 530

Extremophiles, 1314, 21. See also Archaebacteria.

Extrinsic concentration, 202

F

F (fertility) factor, 256257

Facilitated diffusion, 135137

Facultative autotrophs, 52

Facultative organisms, 14

Fall armyworm (Spodoptera frugiperda), 480

Fats in cell construction, 4245

Fatty acids

in cell construction, 4245

definition, 42

examples, 42

fats, 42

FDA (Food and Drug Administration), 1011

Fed-batch bioreactors, 288293

Feedback inhibition, 133, 135

Feedback repression, 130, 135

Fermentation

active, measuring, 349352

definition, 161

glycolysis, 149

molds, 27

penicillin production, 5, 7

two-phase, 489

Fermenter, 324. See also Bioreactor.

Fibrous proteins, 30

Filter sterilization, 361

Filtration, separation of soluble products

cross-flow filtration, 398403

cross-flow ultrafiltration, 398403

diafiltration, 403

MF (microporous filtration), 395398

microfiltration, 395403

rejection coefficient of an ultrafilter, 399400

tangential flow filtration, 398403

UF (ultrafiltration), 395398, 403

Fission reproduction, microscopic eucaryotes, 25

Fixed solids, biological waste treatment, 551

Flagella, 2425

Flagellate motion, 27

Flagellated organisms vs. ciliated organisms, 25

Flagellates, 27

Flat sheet membranes, separation of soluble products, 400402

Flatbed reactors, 530

Fleming, Alexander, 4, 590

Flocculation, separation of insoluble products, 382

Florey, Howard, 4

Fluidized bed reactors, 530

Fluorescence, 165

Foaming, bioreactor scale-up, 328

Food and Drug Administration (FDA), 1011

Fourier transform infrared (FTIR), 352

Freeze drying, purification process, 423

French presses, separation of insoluble products, 383

Freundlich adsorption isotherm, separation of soluble products, 403404

Friable calli in plant cell cultivation, 459

Frontal chromatography, 409

FTIR (Fourier transform infrared), 352

Full inhibition, 134

Fumarate, converting to L-aspartate, 102

Functional genomics, 267

Fungi

ascomycetes, 27

basidiomycetes, 27

definition, 25

deuteromycetes, 27

genetic engineering, host-vector systems, 478

modes of sexual reproduction, 27

phycomycetes, 27

G

G (guanine), 45, 47

Gametes, 23

Gaseous fuels from biomass, 597598

Gases, sterilizing, 362364

Gateway cloning, 262

Gateway sensors, 354

Gaulin–Manton presses, separation of insoluble products, 383

Gelation of polymers, 299

Gel-filtration chromatography, 410411, 414415

Gene bank, 264265

Gene libraries, generating, 512513

Gene library, 264265

Gene therapy using viral vectors, 523528

Gene transfer and rearrangement. See also Mutations.

competent strains, 254

conjugation, 256257

donor DNA, 253

episomes, 256257

F (fertility) factor, 256257

generalized transduction, 254255

genetic recombination, 252254

internal gene transfer, 257

lysogenic cells, 255

main mechanisms, 252. See also specific mechanisms.

plasmid vectors, 254

prophage conversion, 256

restriction endonucleases, 253

specialized transduction, 255

temperate phages, 256

transduction, 254256

transformation, 254

transposons, 257

Generalized transduction, gene transfer and rearrangement, 254255

Genes, 116117

Genetic code

anticodons, 125

codons, 116117, 123

degenerate code, 123

description, 116117, 123124

nonsense codons, 123124

Genetic engineering. See also Mutations.

baculovirus, 265

biolistic processes, 265266

biopharmaceutical products, 473

cer locus, 493

directed evolution, 512

DNA shuffling, 512513

electroporation, 265

error-prone PCR, 512

generating gene libraries, 512513

genome engineering, 266267

of higher organisms, 265266

metabolic control theory, 510

metabolic engineering, 506509

metabolic flux analysis, 510

origins of replication, 490

overview, 258

par locus, 493

plasmid design problems, 490493

promoters, 490491

protein engineering, 511513

protein products vs. nonprotein products, 472474

protoplast fusion, 265

protoplasts, 265

random mutagenesis, 512

rational design, 512

regulatory constraints on, 503506

runaway replication, 490

semirational design, 513

site-directed mutagenesis, 512

synthetic biology, 509511

systems biology, 509511

transfection, 265266

Genetic engineering, basic elements

alternative cloning strategies, 262263

amplifying DNA, 260

cDNA (complementary DNA), 260

cell-surface display, 265

chemical gene synthesis, 259

codon harmonization, 259

codon optimization, 259

DNA microarray technology, 259

electrophoresis, 263264

expressed DNA, 262

expression of cloned genes, 263265

Gateway cloning, 262

gene bank, 264265

gene library, 264265

Gibson assembly, 262

Golden Gate cloning, 263

GreenGate cloning, 263

hybridization, 259

immunoblot testing, 264

inserting genes into DNA, 260262

introns, 259

isothermal cloning, 262

LIC (ligation independent cloning), 263

ligands, 265

MoClo (molecular cloning), 263

obtaining the gene of interest, 259260

overview, 258

PCR (polymerase chain reaction), 260

phage display, 265

plasmid vectors, 260

probes, 259

recombinant DNA techniques, 258

restriction endonuclease, 262263

restriction enzymes, 259260

reverse transcriptase, 260

shotgun cloning, 259, 264

synonymous mutations, 259

TA cloning, 262

testing for proteins, 264

TOPO cloning, 262

type IIS enzyme, 262263

Western blot testing, 264

yeast-mediated cloning, 263

Genetic engineering, genetic instability

dimers, 487

growth-rate-dominated instability, 489490

high-copy-number plasmids, 486

host cell mutations, 488489

host-vector interactions, 493503

low-copy-number plasmids, 486

metabolic burden, 489

multimers, 487

overview, 486

plasmid structural instability, 488

segregational loss, 486488

selective pressure, 489

tetramers, 487

two-phase fermentation, 489

Genetic engineering, host-vector systems, 474

A. nidulans, 478

B. subtilis, 477

baculovirus (Autographa californica), 480

cabbage looper (Trichoplusia ni), 480

CFPS (cell-free protein synthesis), 484

CHO (Chinese hamster ovary) cells, 479480, 484485

comparison of strategies, 484485

continuous cells, 479

CRISPR (clustered regularly interspaced short palindromic repeat), 480

E. coli, 475477, 484485

fall armyworm (Spodoptera frugiperda), 480

fungi, 478

gram-positive bacteria, 476

H. polymorpha, 478

heat shock, 475

heterologous hosts, 507508

identification of pathway enzymes, 508509

immortal cells, 479

inclusion bodies, 475

insect cell–baculovirus system, 480482

L. lactis, 477

lower eucaryotic cells, 477479

mammalian cells, 479480

native hosts, 508

NOVs (nonoccluded viruses), 481

overview, 474475

P. pastoris, 478

protein secretion/excretion, 476

S. cerevisiae, 477478

signal peptides, 476

Streptomyces, 477

transformed cells, 479

transgenic animals, 482483

transgenic plants and plant cell culture, 483484

yeasts, 478

Genetic instability. See Genetic engineering, genetic instability.

Genetic recombination, gene transfer and rearrangement, 252254

Genetic-level control, 130133

Genome engineering. See also Genetic engineering; Genomics.

CRISPR (clustered regularly interspaced short palindromic repeat), 267

customizing meganucleases, 266267

eliminating genes, 266

introducing targeted modifications into chromosomes, 266

MAGE (multiplex automated genome engineering), 266

molecular scissors, 266

protein engineering, 266267

Genomes

definition, 15, 267

editing. See Genome engineering; Genomics.

Genomics. See also Genome engineering.

bioinformatics, 271

BLAST (basic local alignment search tool), 271

computational techniques, 271

definition, 267

functional, 267

homologous amino acid sequences, 271

ORFs (open reading frames), 271

overview, 267

proteomics, 267

systems biology, 267

Genomics, experimental techniques

cost of sequencing a complete genome, 270

high-throughput sequencing, 269

Illumina sequencing, 269

isoelectric points, 270

microarrays, 270

nanopores, 269

NGS (next-generation sequencing), 269

overview, 268270

Sanger sequencing, 267268

SBS (sequencing by synthesis) sequencing, 269

transcriptomics, 270

two-dimensional gel electrophoresis, 270

Genotype, definition, 248

Genus, 15

Gibson assembly, 262

Glass wool filters, 362

Globular proteins, 30

GLP (good laboratory practices), 10

Glucanases, 102

Gluconeogenesis, 160

Glucose

catabolism, 149152

converting to fructose, 102

Glucose effect, 131

Glucose metabolism, 149152

Glycans, 24, 36, 42, 127

Glycoforms, 127129

Glycogen, 41

Glycolysis

aerobic respiration, 149

anaerobic respiration, 149

citric acid cycle, 149

electron transport chain, 149, 152154

fermentation, 149

phases, 149

respiration, 149

TCA (Krebs, tricarboxylic acid), 149

Glycosylation, 24, 42, 115, 127

Glyoxysomes, 24, 433

GMP (good manufacturing process), 10

Golden Gate cloning, 263

Golgi apparatus, 127

Golgi bodies, 24, 433

Golgi trans face, 127

Gompertz equation, 200201

Good laboratory practices (GLP), 10

Gram, Hans Christian, 18

Gram staining

bacteria, 18

colorless reaction, 18

eubacteria (true bacteria), 18

negative reaction, 18. See also E. coli.

no reaction, 19

positive reaction, 18. See also B. subtilis.

procaryotes, 20

purple reaction, 18

red reaction, 18

Gram-positive bacteria, 476

GreenGate cloning, 263

Group translocation, 135137

Growing cells. See Cell growth.

Growth dynamics of animal cells, 441443

Growth media, animal cell cultivation, 437441

Growth-associated products, 183

Growth-rate-dominated instability, 489490

Grow-through tests, 363

GTP (quanosine triphosphate), 45

Guanine (G), 45, 47

H

H. polymorpha, 478

Hairy roots, bioreactor considerations in plant cell cultivation, 466467

Haldane, J. B. S., 66

Half-velocity constant, 192193

Halophiles, 14, 21

Hanes–Woolf plot, 6970

Haploid cells, 23

HC (hydrophobic chromatography), 411

Heat generated by microbial growth, 190191

Heat shock, 475

Heat shock regulon, 131132

Heat transfer, 331337

Heatley, Norman, 4

Helical structures in proteins, 3334

Hematopoiesis, 529530

Hemicellulases, 102

Hemocytometer, 171

Henri, V. C. R., 63

Heterologous hosts, 507508

Heterotrophs, 52

HFCS (high-fructose corn syrup) production, 593595

HIC (hydrophobic interaction chromatography), 411

High-copy-number plasmids, 486

High-pressure liquid chromatography (HPLC), 352, 411

High-throughput sequencing, 269

Hindered settling, separation of insoluble products, 378380

Histones, 22

HIV (human immunodeficiency) virus, reverse transcription, 115

HMP (hexose monophosphate) pathway, 158161

H/O (proton/oxygen) ratio, 229

Hollow fiber membranes, separation of soluble products, 400402

Hollow-fiber reactors, 445

Holoenzymes, 61, 119

Homologous amino acid sequences, 271

Hormones, 139

Host cell mutations, 488489

Host-vector interactions, 493503

HPLC (high-pressure liquid chromatography), 352, 411

Hughes press, separation of insoluble products, 384

Humoral immune response, 36

Hybrid bioreactors, 311313

Hybrid glycoforms, 129

Hybridization, 259

Hybridoma cells, 436

Hydrocarbons, metabolism of, 156157

Hydrogen gas production, 597598

Hydrogen macronutrient, 53

Hydrophobic chromatography (HC), 411

Hydrophobic interaction chromatography (HIC), 411

Hydroxylation, 116

Hypervariable regions, 36

Hyphae, 25

I

IEC (ion-exchange chromatography), 410411, 414, 419420

IEM (ion-exchange membranes), 421

Illumina sequencing, 269

IMAC (immobilized-metal-affinity chromatography), 416419

Immobilized cell systems

active cell immobilization, 298302

binding, 300302

biological films, 303304

bioreactor considerations, 309311

cell adsorption, 300301

covalent binding, 301302

diffusional limitations, 304308

encapsulation, 300

entrapment, 298300, 302

gelation of polymers, 299

ion-exchange gelation, 299

microbial flac, 305

overview, 298

passive immobilization, 303304

polycondensation, 299

polymerization, 299

precipitation of polymers, 299

three-dimensional printing, 300

Immortal cells, 435, 479

Immunoblot testing, 264

Immunoglobulins, 3437

Immunotherapy, 36

Impellers, 324325

Inclusion bodies, 475

Incompressible cake, 376378

Indirect methods of counting cells, 172175

Indirect selection mutation, 250

Induced fit model, enzymes, 63

Induced pluripotent stem (iPS) cells, 529

Inducer exclusion, 131

Inducers, 130

Induction, 130

Industrial uses for

enzymes, 100103

mixed culture biological waste treatment, 546548

Industrial wastes, biological waste treatment, 549

Inhibitors, enzyme kinetics, 7374

Initial-rate experiments, 6768

Initiation complex, 125

Initiation factors, 125

Initiation step, 124125

Inner membranes

E. coli, 18

eucaryotes, 23

Insect cell–baculovirus system, 480482

Insect cells, cultivating, 435436

Insertable probes, 349351

Inserting genes into DNA, 260262

Insertion-sequence (IS) elements, 248

Insoluble substrates, 8384

Integral member proteins, 43

Integral membrane in proteins, 30

Inteins, 116

Intermediate filaments, 25, 433

Internal gene transfer, 257

Internal mechanical agitation, 324329

Internal mechanical agitation bioreactors, 324329

Internal membrane bioreactors, 295

Interphase, 23

Intracellular spores, 20

Intrinsic concentration, 202

Introns, 116, 121122, 259

Ion-exchange gelation, 299

Ion-exchange membranes (IEM), 421

Ion-exchanging chromatography (IEC), 410411, 414, 419420

iPS (induced pluripotent stem) cells, 529

Irreversible inhibitors, enzyme kinetics, 73

IS (insertion-sequence) elements, 248

Isoelectric focusing, 420

Isoelectric points, 32, 270

Isoelectric precipitation, 390392

Isofunctional enzymes, 134

Isothermal cloning, 262

Isozymes, 61, 134

J

Junk DNA. See Coding DNA.

K

Ketones, 36

Kinetics

batch cell growth. See Batch cell growth kinetics; Models of cell growth kinetics.

death, 356357

Michaelis–Menten. See Michaelis–Menten kinetics.

Km, interpreting, 7071

Koji process, 314

Krebs tricarboxylic acid (TCA) cycle, 149152

L

L. lactis, 477

lacA gene, 130

Lactases, 102

Lactic acid production, 581584

Lactose, 40

LacY enzyme, encoding, 131

lacY gene, 130

lacZ gene, 130

Lag phase, 175177

Lagging strands, 118

Langmuir isotherm, 404

Langmuir–Hinshelwood kinetics, 63

Latin names, 15

Leading strands, 118

LIC (ligation independent cloning), 263

Ligands, 55, 265

Ligation independent cloning (LIC), 263

Light phase of photosynthesis, 164

Lineweaver–Burk plot, 68

Lipases, 101

Lipidation, 116

Lipids

in cell construction, 4245

PHA (polyhydroxyalkanoates), 44

PHB (polyhydroxybutyrate), 44

steroids, 4445

Lipoglycans. See LPS (Lipopolysaccharide).

Lipopolysaccharide (LPS), 18

Liquid fuel production, 596597

Liquid–liquid extraction, 385389

Liquids, sterilizing, 357362

LLC (liquid–liquid partition chromatography), 410411

LncRNA (long ncRNA), 49

Lock-and-key model, enzymes, 63

Logarithmic growth phase. See Exponential growth phase.

Logistic equations, 197200

Long ncRNA (lncRNA), 49

Loop reactors, scaling up, 329330

Lotka–Volterra model of mixed culture interactions, 542545

Low-copy-number plasmids, 486

Lower eucaryotic cells in genetic engineering, host-vector systems, 477479

LPS (Lipopolysaccharide), 18

LPS removal, 18

Luedeking–Piret equation, 183

Lumenal phase cytoplasm, 432

Lypophilization, purification process, 423424

Lysogenic cells, gene transfer and rearrangement, 255

Lysogenic cycle of viruses, 17

Lysosomes, 24, 432

Lysozyme, uses for, 102

Lytic cycle of viruses, 17

M

Macronutrients

autotrophs, 52

carbon compounds, 5253

categories of microorganisms, 52

chemautotrophs, 52

definition, 51

elements of, 5354

facultative autotrophs, 52

heterotrophs, 52

hydrogen, 53

magnesium, 53

mixotrophs, 52

nitrogen, 5253

oxygen, 53

phosphorus, 53

photoautotrophs, 52

potassium, 53

sulfur, 53

MAGE (multiplex automated genome engineering), 266

Magnesium, macronutrient, 53

Maintenance, 180

Maintenance coefficient, 213

Maintenance energy, 178

Mammalian cell culture, 436437

Mammalian cells in genetic engineering, host-vector systems, 479480

Maximum growth potential, 200201

Medical uses for

bioprocess engineering. See Bioprocess engineering, medical uses for.

enzymes, 100103

Membrane bioreactors, 294297

Membrane configurations, separation of soluble products, 400402

Membrane-based units, 530

Menten, M. L., 63

Merck, producing penicillin, 56

Mesophiles, 14

Messenger (mRNA), 4850

Metabolic burden, 489

Metabolic control theory, 510

Metabolic engineering

definition, 2, 145

heterologous hosts, 507508

host selection, 506508

identifying pathway enzymes, 508509

native hosts, 508

overview, 506

Metabolic flux analysis, 510

Metabolic pathway control, 133135

Metabolic pathways

anabolism, definition, 146

anaerobic metabolism, 161163

autotrophic metabolism, 163165

biodegradation of xenobiotics (toxic aromatic compounds), 157158

bioenergetics, 146148

biosynthesis, 158161

Calvin cycle, 163165

control sites in aerobic glucose metabolism, 154155

Crabtree effect, 146

dark phase, 164

degrading compounds into simpler products. See Catabolism.

EMP (Embden–Meyerhof–Parnas) pathway, 149152

glucose metabolism, 149152

glycolysis, 149152

light phase, 164

metabolic engineering, definition, 145

metabolism of hydrocarbons, 156157

metabolism of nitrogenous compounds, 155156

NADH, functions in biological systems, 148

nitrogen fixation, 156

nitrogenase, 156

overview, 145

Pasteur effect, 155

respiration, 152154

synthesizing complex compounds. See Anabolism.

TCA cycle, 149152

Metabolic regulation

basal level of proteins, 131

catabolite repression, 131

concerted feedback inhibition, 134

constitutive genes, 132

cooperative feedback inhibition, 134

cumulative feedback inhibition, 134

diauxic growth, 132

end-product inhibition, 133

enhancer regions, 131

enzyme induction, 131

feedback inhibition, 133, 135

feedback repression, 130, 135

full inhibition, 134

genetic-level control, 130133

glucose effect, 131

heat shock regulon, 131132

inducer exclusion, 131

inducers, 130

induction, 130

isofunctional enzymes, 134

isozymes, 134

lacA gene, 130

LacY enzyme, encoding, 131

lacY gene, 130

lacZ gene, 130

metabolic pathway control, 133135

operator regions, 130

operons, 130

permease, encoding, 131

proteins synthesized, 130133

regulons, 131

sequential feedback inhibition, 134

unregulated genes. See Constitutive genes.

Metabolism

of nutrients in animal cells, 433434

role of cells, 137139

Methane production, 564, 597598

MF (microporous filtration), 395398

MFCs (microbial fuel cells), 598600

Michaelis, L., 63

Michaelis–Menten kinetics

vs. allosteric kinetics, 72

overview, 6365

Michaelis–Menten kinetics, determining rate parameters

batch kinetics, 6970

double-reciprocal plot, 68

Eadie–Hofstee plot, 6869

Hanes–Woolf plot, 6970

initial-rate experiments, 6768

interpretation of Km and Vm, 7071

Lineweaver–Burk plot, 68

Microarrays, 270

Microbes, compared to plant cell cultivation, 457462

Microbial flac, 305

Microbial products, classifying, 183184

Microencapsulation, 87

Microfiltration, separation of soluble products, 395403

Micronutrients

categories, 54

chelating agents, 55

commonly added, 54

definition, 51

growth factors, 55

ligands, 55

rarely added, 55

sometimes added, 5455

Microorganisms

categories of, 52

naming, 15

Microphysiological systems, 531

Microporous filtration (MF), 395398

Microreactors, 342348

Microscopic eucaryotes. See Eucaryotes, microscopic.

Microtubules, 25, 433

Microvilli, 432

Minkevich, I. G., 229

miRNA (microRNA), 49

Mitochondria, 2324, 432

Mitosis, 23

Mixed and forcefully aerated bioreactors, 314

Mixed culture, biological waste treatment

acid formers, 564

activated-sludge processes, 551553

adsorbent-added activated-sludge process, 557558

advanced process, 566571

agricultural wastes, 549

anaerobic digestion, 564566

Bardenpho process, 571

basic process, 551566

biological treatment, 549

BOD (biological oxygen demand), 550

CFSTR (continuous-flow, stirred-tank reactor), 552

chemical treatment, 549

COD (chemical oxygen demand), 550

contact stabilization, 557

converting wastewater to useful products, 571572

domestic wastes, 549

fixed solids, 551

formation of methane, 564

formation of volatile acids, 564

industrial uses, 546548

industrial wastes, 549

MLSS (mixed-liquor suspended solids), 551

MLVSS (mixed-liquor volatile suspended solids), 551

modified activated sludge processes, 556563

nitrification, 567568

oxidation ponds, 563564

oxygen enriched air, 558

PEKILO process, 571572

PFRs (plug flow reactors), 552

physical treatment, 549

RBC (rotating biological contactor), 561563

shock loading, 552553

sludge bulking, 553556

sludge re-aeration, 556557

solubilization of insoluble organics, 564

stop feeding/stop aeration, 556

SYMBA process, 571572

TKN (total Kjeldahl nitrogen), 551

TOD (total organic carbon), 550

treatment, types of, 549

trickling biological filters, 558561

types of. See also specific types.

typical steps, 551

UCT process, 571

UNOX process, 552, 558

VIP process, 571

volatilized material, 551

wastes, types of, 549. See also specific types.

wastewater characteristics, 549551

Mixed culture, industrial uses for

SYMBA process, 548

waste treatment, 546548

whiskey manufacturing, 546

Mixed culture in nature, 545546

Mixed culture interactions

amensalism, 538539

commensalism, 538

competition, 536

mutualism, 537538

neutralism, 537

parasitism, 539

predation, 539

protocooperation, 537538

same growth limiting substrate, 536537

symbiosis, 538

Mixed culture interactions, models of

Lotka–Volterra, 542545

mutualism, 541542

overview, 539540

prey–predator, 542545

same growth limiting substrate, 540541

Mixed inhibition, enzyme kinetics, 76

Mixed-growth-associated product formation, 183

Mixotrophic cultures, 467

Mixotrophs, 52

MLSS (mixed-liquor suspended solids), 551

MLVSS (mixed-liquor volatile suspended solids), 551

Mobile phase chromatography, 409

MoClo (molecular cloning), 263

Models of cell growth kinetics

for filamentous organisms (molds), 201

with growth inhibitors, 195197

with time delays, 202

for transient behavior, 201202

Modified activated sludge processes, 556563

Molds

conidia, 25

definition, 25

fermentation method, 27

hyphae, 25

mycelium, 25

reproduction model, 26

size, 25, 27

uses for, 27

Molecular scissors, 266

Molecular sieving chromatography, 410, 414415

Monod equation, 192194, 197

Monosaccharides, 3840

Moromi culture, 314

Mortal cells, 435

Moser equation, 194

Motion, protozoa, 27

Moving-bed columns, separation of soluble products, 404

mRNA, 4850, 116, 121122

Multimers, 487

Multiorgan-on-a-chip systems, 531

Multiphase enzymatic reactions, 8485

Multiplex automated genome engineering (MAGE), 266

Multistage chemostat bioreactor, 281287

Mutagens, 250

Mutations. See also Gene transfer and rearrangement; Genetic engineering.

in chemostats, 217

definition, 247248

expressed characteristics. See Phenotype.

genetic construction. See Genotype.

genotype, 248

phenotype, 248

wild type, 248

Mutations, mechanisms of genetic change

back mutations, 248249

deletion mutations, 248

IS (insertion-sequence) elements, 248

nonsense mutations, 248

point mutations, 248

reading frame, 248

reversions, 248249

silent mutations, 248

suppressor mutations, 249

Mutations, selecting for desirable

auxotrophic mutants, 250251

chemical agents, 250

conditional mutants, 251

direct selection, 250

indirect selection, 250

mutagens, 250

natural rates of mutation, 250

replica plating, 251

selectable mutations, 250

spontaneous rates of mutation, 250

unselectable mutations, 250

Mutualism, 537538, 541542

Mycelium, 25

Mycoplasma, 19

N

NAD (nicotinamide adenine dinucleotide), 45

NADH, functions in biological systems, 148

NADP (nicotinamide adenine dinucleotide phosphate), 45

Naming enzymes, 61

Nanopores, 269

Native hosts, 508

Natural amino acids, 31

Natural rates of mutation, 250

ncRNA (noncoding), 49, 51

Neutralism, 537

Neutrophiles, 14

Next-generation sequencing (NGS), 269

NGS (next-generation sequencing), 269

Nicotinamide adenine dinucleotide (NAD), 45

Nicotinamide adenine dinucleotide phosphate (NADP), 45

Nitrification, biological waste treatment, 567568

Nitrogen, macronutrient, 5253

Nitrogen fixation, 156

Nitrogenase, 156

Nitrogenous compounds, metabolism of, 155156

N-linked glycosylation, 129

Nonanchorage-dependent cells, 435

Noncoding (ncRNA), 49, 51

Noncoding DNA, 49

Noncompetitive inhibitors, enzyme kinetics, 73, 7475

Nongrowth-associated product formation, 183

Nongrowth-related functions, 181182

Nonoccluded viruses (NOVs), 481

Nonprotein products vs. protein products, 472474

Nonsense codons, 123125

Nonsense DNA, 122

Nonsense mutations, 248

Nonstirred reactor systems, 444445

Normal phase chromatography, 410

NOVs (nonoccluded viruses), 481

Nucleic acids in cell construction, 4451

Nucleoli, 433

Nucleotides. See also DNA (deoxyribonucleic acid); RNA (ribonucleic acid).

A (adenine), 45, 47

AMP (adenosine monophosphate), 45

ATP (adenosine triphosphate), 45

C (cytosine), 45, 47

G (guanine), 45, 47

GTP (quanosine triphosphate), 45

major components, 45

NAD (nicotinamide), 45

NAD (nicotinamide adenine dinucleotide), 45

NADP (nicotinamide adenine dinucleotide phosphate), 45

structure of, 46

T (thymine), 45, 47

U (uracil), 45

Nucleus, eucaryotes, 22

O

Okazaki fragments, 118

Oligosaccharyltransferase (OST), 129

Open reading frames (ORFs), 271

Operator regions, 130

Operons, 130

Optical density of cell cultures, 172

ORFs (open reading frames), 271

Organized tissues, bioreactor considerations in plant cell cultivation, 466467

Orientation effect, 63

Osmosis, separation of soluble products, 393

Osmotic shock, separation of insoluble products, 384385

OST (oligosaccharyltransferase), 129

OTR (oxygen transfer rate), 188

OUR (oxygen uptake rate), 188

Outer membrane, E. coli, 18

Oxidation ponds, biological waste treatment, 563564

Oxidation-reduction half-reactions, 237240

Oxidative phosphorylation, 152154

Oxygen

concentration for batch cell growth kinetics, 187188

enriched air biological waste treatment, 558

macronutrient, 53

solubility, bioreactor scale-up, 332335

Oxygen removal

dynamic method, 335

steady-state method for, 334

unsteady-state method for, 333

P

P. pastoris, 478

Pacific Yew tree, 456457

Packed cell volume, 172

Packed-bed bioreactors, 314

Packed-bed columns, separation of soluble products, 404

par locus, 493

Parasitism, model of mixed culture interaction, 539

Particle counters, 171

Partition coefficient, 85

Passive diffusion, 135137

Passive immobilization, 303304

Pasteur effect, 155

Pathway enzymes, identifying, 508509

PBPK (physiologically based pharmacokinetic) model of the human body, 531

PCR (polymerase chain reaction), 260

Pectinases, 100

PEKILO process, 571572

Penicillin

discovery of, 45

WW II poster, 8

Penicillin acylase, 102

Penicillin production

aerobic bioprocesses, 590592

bottle plant, 6

chemical synthesis, 5

fermentation, 5, 7

Merck, 56

Pfizer, 56

schematic of, 9

Squibb, 5

submerged tank process, 6

surface method, 6

USDA Northern Regional Research Laboratory, 56

Pentose-phosphate, 158161

Peptide bond, 32

Peptides, forming from RNA. See DNA translation.

Peptidoglycan, 18

Peptidyl site, 125

Perfusion systems bioreactor, 293294

Perinuclear space, 433

Peripheral member proteins, 43

Periplasmic space, 18

Periwinkle to ajmalicine, 465

Permease, encoding, 131

Peroxisomes, 24, 433

Petroff–Hausser counting chamber, 171

Pfizer, producing penicillin, 56

PFRs (plug flow reactors), 208, 210, 552

pH effects

batch cell growth kinetics, 186

on enzyme kinetics, 8082

pH effects on cells and their environments

pH values 1 or 2. See Acidophiles.

pH values 6 to 8. See Neutrophiles.

pH values above 9. See Alkaliphiles.

PHA (polyhydroxyalkanoates), 44

Phage display, 265

Phages (bacteriophages), 17

PHB (polyhydroxybutyrate), 44

Phenotype, definition, 248

Phosphoglycerides in cell construction, 43

Phospholipids in cell construction, 43

Phosphorus, macronutrient, 53

Phosphorylation, 116

Phosphotransferase system, 137

Photoautotrophs, 52

Photoperiod control, 467

Photophosphorylation, 165

Photosynthesis

bacteria, 20

carbohydrates, 36

eubacteria (true bacteria), 19

eucaryotes, 24

Phototaxis, 138

Physical environment, monitoring, 350

Physical treatment, biological waste treatment, 549

Physiologically based pharmacokinetic (PBPK) model of the human body, 531

Plant cell cultivation

aggregates, 460

anticancer agent (Taxol), 456457

callus cultures, 458459

common products from, 452456

compared to microbes, 457462

differentiated tissue, 459

economics of, 467468

elicitors, 460461

friable cali, 459

Pacific Yew tree, 456457

plasmodesmata, 460

suspension cultures, 458459

totipotency, 457461

volumetric productivities, 468

Plant cell cultivation, bioreactor considerations

ajmalicine from periwinkle, 465

cell immobilization, 463465

hairy roots, 466467

mixotrophic cultures, 467

organized tissues, 466467

photoperiod control, 467

root mats, 467

submerged culture, 467

suspension cultures, 462463

Plant vs. animal eucaryotes, 22

Plasmid vectors

gene transfer and rearrangement, 254

inserting genes into DNA, 260

Plasmids

definition, 48

design problems, 490493

structural instability, 488

Plasmodesmata in plant cell cultivation, 460

Plate counts, 171

Plug flow reactors (PFRs), 208, 210, 552

Pluripotent stem cells, 529

Pneumatic conveyor dryers, purification process, 424

P/O ratio, 153154, 229

Point mutations, 248

Polyadenylation, 122

Polycondensation, 299

Polygenic messages, 121

Polyhydroxyalkanoates (PHA), 44

Polyhydroxybutyrate (PHB), 44

Polymerase chain reaction (PCR), 260

Polymerization, 299

Polymers, precipitating, 299

Polypeptides, amino acids in, 31

Polysaccharides, 4042

Posttranslation movement across membranes, 125

Posttranslational modification of cells, 115116

Posttranslational modifications (PTMs), 127

Posttranslational processing, 125129

Potassium, macronutrient, 53

Precipitation

of polymers, 299

separation of soluble products, 390392

Precipitin, 36

Predation model of mixed culture interaction, 539

Prey–predator model of mixed culture interactions, 542545

Primary culture of cells, 434435

Primary metabolites, 178

Probability of extinction, 356

Probe drift, 351

Probe fouling, 351

Probes, 259, 349351

Procaryotes. See also Eucaryotes.

archaebacteria, 15

BMCs (bacterial microcompartments), 20

definition, 15

vs. eucaryotes, 16, 22

nomenclature, 15

ribosomes, 20

shape, 18

size, 18

spores, 20

staining, 20

storage granules, 20

structures, 20

subdivisions. See Archaebacteria; Eubacteria (true bacteria).

volutins, 20

Procaryotic cells

vs. eucaryotic cells, DNA transcription, 121122

posttranslational protein release, 127

Process validation, FDA, 1011

Progenitor cells, 529

Promoter region, 121

Promoters, 490491

Prophage conversion, 256

Prosthetic groups, 3233

Proteases, 100

Protective proteins, 31

Protein engineering, 266267, 511513

Protein products vs. nonprotein products, 472474

Protein release, 127

Protein secretion/excretion, 476

Protein splicing, 116

Proteinogenic amino acids, 31

Proteins. See also Amino acids.

Ag (antigen) macromodule, 34, 36

basal level, 131

biological functions, 29

building blocks of, 31. See also Amino acids.

catalytic, 30

definition, 29

fibrous, 30

forming from RNA. See DNA translation.

globular, 30

helical structures, 3334

humoral immune response, 36

immunoglobulins, 3437

immunotherapy, 36

integral membrane, 30

primary structure, 33

prosthetic groups, 3233

protective, 31

quaternary structure, 33

regulatory, 31

secondary structure, 33

structural, 30

structure of, 29

synthesized, 130133

tertiary structure, 33

three-dimensional structure, 3334

transport, 30

Proteins, antibodies

Ab (antibody) macromodule, 34

ADC (antibody-drug conjugate), 36

antibody–antigen complex, 36

antibody–antigen interaction, 36

CDRs (complementarity determining regions), 36

description, 3436

engineered antibodies, 36

glycans, 36

hypervariable regions, 36

Proteomics, 267

Protocooperation, 537538

Proton-motive forces, 136137

Proton/oxygen (H/O) ratio, 229

Protoplast fusion, 265

Protoplasts, 265

Protozoa

ameboid motion, 27

amoebae, 27

cilia, 27

ciliates, 27

definition, 2728

diseases caused by, 28

flagellate motion, 27

flagellates, 27

motion, 27

sporozoans, 27

trypanosomes, 27

wastewater treatment, 28

Proximity effect, 63

Psychrophiles, 14

PTMs (posttranslational modifications), 127

Purification

costs, 371372

crystallization, 422423

drying, 423424

freeze drying, 423

lypophilization, 423424

major steps in, 373

major units of operation, 372373

pneumatic conveyor dryers, 424

rotary-drum dryers, 424

separation of soluble products, 403

spray dryers, 424

vacuum-tray dryers, 423

Purple and green bacteria. See Anoxygenic photosynthetic bacteria.

Pyrrolysine, 31

Q

Quanosine triphosphate (GTP), 45

Quasi-steady-state assumption, 6667

Quaternary structure, proteins, 33

R

Random mutagenesis, 512

Rannie high-pressure homogenizer, 383

Rapid-equilibrium assumption, 6566

Rarely added micronutrients, 55

Rate of substrate transfer (RST), 85

Rational design, 512

RBC (rotating biological contactor), 561563

Reaction, integrating with separation, 424425

Reactor. See Bioreactor.

Reading frame, 248

Reading through a terminator, 121

Recombinant DNA techniques, 258

Recovery. See also Separation.

costs, 371372

major steps in, 373

major units of operation, 372373

Redox potential, batch cell growth kinetics, 189

Reflection coefficient, separation of soluble products, 394

Regenerative medicine, 519523

Registering this book, xviii

Regulated exocytosis pathway, 127

Regulatory constraints on genetic engineering, 503506

Regulatory enzymes, 30

Regulatory proteins, 31

Regulatory RNA, 49

Regulons, 131

Rejection coefficient of an ultrafilter, 399400

Release factor (RF), 125

Replica plating, 251

Replication

of cells, 114

DNA. See DNA replication.

origins of, 490

runaway, 490

Replication forks, 117

Reproduction model of molds, 26

Reproduction of viruses, 17

Research approaches, biologists vs. engineers, 3

Respiration

electron transport chain, 149, 152154

glycolysis, 149

oxidative phosphorylation, 152154

P/O ratio, 153154

Restriction endonucleases, 253, 262263

Restriction enzymes, 259260

Retrotransposons, 115

Retroviruses. See also Viruses.

mass production of, 527528

reverse transcription, 115

Reverse osmosis (RO), 393395

Reverse transcriptase, 115, 260

Reverse transcription, 115

Reversible inhibitors, enzyme kinetics, 73

Reversions, 248249

RF (release factor), 125

Rho protein, 121

Ribonucleic acid (RNA). See RNA (ribonucleic acid).

Ribonucleotides, structure of, 46

Ribosomal (rRNA), 49, 51

Ribosomes

definition, 49

number per cell, 20

in procaryotes, 20

Ribozymes, 61

RNA (ribonucleic acid). See also DNA (deoxyribonucleic acid); Nucleic acids.

building blocks of. See Nucleotides.

carrying genetic information, 4849

coding, 48

definition, 49

forming peptides and proteins. See DNA translation.

long ncRNA (lncRNA), 49

messenger (mRNA), 4850

microRNA (miRNA), 49

mRNA splicing, 116

noncoding (ncRNA), 49, 51

regulatory, 49

replication, 115

ribosomal (rRNA), 49, 51

ribozymes, 61

RNA silencing, 115

RNA-dependent RNA polymerases, 115

small interfering (siRNA), 49

structure of, 47

transfer (tRNA), 4950

RNA polymerase enzyme, 119

RNA primer, 117118

RNA silencing, 115

RNA-dependent RNA polymerases, 115

RO (reverse osmosis), 393395

Roche 454 sequencing, 269

Rod (bacillus) cells, 14

Root mats, bioreactor considerations in plant cell cultivation, 467

Rotary vacuum precoat filters, 374

Rotary-drum dryers, purification process, 424

Rotating biological contactor (RBC), 561563

Rotating-drum bioreactors, 314

rRNA, 49, 51, 121

RST (rate of substrate transfer), 85

Runaway replication, 490

Rupture with ice crystals, separation of insoluble products, 384385

Rushton impeller, 325

S

S. cerevisiae, 25, 477478

Salting out, separation of soluble products, 390391

Same growth limiting substrate, 536537, 540541

Sanger, Frederick, 267

Sanger sequencing, 267268

Saturated zone, separation of soluble products, 405

Saturation constant, 192193

Saturation kinetics, 6365

SBS (sequencing by synthesis) sequencing, 269

Scenedesmus algae, 27

Secondary culture of cells, 435

Secondary metabolites, 178

Segregated models, 191

Segregation, 191

Segregational loss, 486488

Selectable mutations, 250

Selective pressure, 489

Selenosysteine, 31

Semicontinuous bioreactors. See Fed-batch bioreactors.

Semirational design, 513

Senescence, 435

Separation, integrating with reaction, 424425. See also Recovery.

Separation of insoluble products

cake resistance, 376378

cell disruption, mechanical, 383385

cell disruption, nonmechanical, 384385

centrifugation, 378382

centrifugation coefficient, 381

coagulation, 382

Dyno-Mill homogenizer, 384

filtration, 374378

flocculation, 382

French presses, 383

Gaulin–Manton presses, 383

hindered settling, 378380

Hughes press, 384

incompressible cake, 376378

osmotic shock, 384385

Rannie high-pressure homogenizer, 383

rate of filtration, 375

rotary vacuum precoat filters, 374

rupture with ice crystals, 384385

sonicators, 383

ultrasonic vibrators, 383

X-press, 384

Separation of soluble products

adsorption, 403409

adsorption zone, 405

anisotropic membranes, 395

aqueous two-phase affinity partition extraction, 389

aqueous two-phase extraction, 389390

bed depth-service time equation, 405409

centrifugal Podbielniak extractors, 387388

concentration, 403

concentration polarization, 394395

cross-flow filtration, 398403

cross-flow ultrafiltration, 398403

diafiltration, 403

dialysis, 392393

dialysis equilibrium, 393

dissociation extraction, 387388

Donnan equilibrium, 393

ED (electrodialysis), 421422

electrophoresis, 419420

flat sheet membranes, 400402

Freundlich adsorption isotherm, 403404

hollow fiber membranes, 400402

IEM (ion-exchange membranes), 421

ionized species. See Dissociation extraction.

isoelectric focusing, 420

isoelectric precipitation, 390392

Langmuir isotherm, 404

liquid–liquid extraction, 385389

membrane configurations, 400402

MF (microporous filtration), 395398

microfiltration, 395403

moving-bed columns, 404

osmosis, 393

packed-bed columns, 404

precipitation, 390392

purification, 403

reflection coefficient, 394

rejection coefficient of an ultrafilter, 399400

RO (reverse osmosis), 393395

salting out, 390391

saturated zone, 405

solubility reduction, 390391

solvent precipitation, 390392

spiral-wound cartridge membranes, 400402

tangential flow filtration, 398403

UF (ultrafiltration), 395398, 403

virgin zone, 405

Separation of soluble products, chromatography

ADC (adsorption chromatography), 410411

AFC (affinity chromatography), 411, 414419

definition, 409

displacement chromatography, 409

elution chromatography, 409

frontal chromatography, 409

gel-filtration chromatography, 410411, 414415

HC (hydrophobic chromatography), 411

HIC (hydrophobic interaction chromatography), 411

HPLC (high-pressure liquid chromatography), 411

IEC (ion-exchanging chromatography), 410411, 414, 419420

IMAC (immobilized-metal-affinity chromatography), 416419

LLC (liquid–liquid partition chromatography), 410411

mobile phase, 409

molecular sieving, 414415

molecular sieving chromatography, 410

normal phase chromatography, 410

size exclusion chromatography, 410

stationary phase, 409

summary of methods, 410411

typical chromatographic column, 411414

Sequencing by synthesis (SBS), 269

Sequential feedback inhibition, 134

Sexual reproduction, eucaryotes, 23

Shock loading, biological waste treatment, 552553

Shotgun cloning, 259, 264

Sigma factor, 119

Signal peptides, 125, 476

Silent mutations, 248

Simple glycoforms, 129

Single-use bioreactors, 330331

Single-use disposable systems, 445, 447

siRNA (small interfering RNA), 49

Site-directed mutagenesis, 512

Size exclusion chromatography, 410

Skin replacement, 521522

Sludge bulking, biological waste treatment, 553556

Sludge re-aeration, biological waste treatment, 556557

Solid-state fermentation (SSF) reactors, 313316

Solubility reduction, separation of soluble products, 390391

Solubilization of insoluble organics, biological waste treatment, 564

Solvent precipitation, separation of soluble products, 390392

Sometimes added micronutrients, 5455

Sonicators, separation of insoluble products, 383

SOP (standard operating procedures), 10

Spargers, 324

Specialized transduction, gene transfer and rearrangement, 255

Specific activity, 7071

Sperm cells, 23

Spherical (coccus) cells, 14

Spiral (spirillum) cells, 14

Spiral-wound cartridge membranes, 400402

Spirillum (spiral) cells, 14

Spirulina algae, 27

Spodoptera frugiperda (fall armyworm), 480

Spontaneous rates of mutation, 250

Spores of procaryotes, 20

Sporozoans, 27

Spray dryers, purification process, 424

Squibb, producing penicillin, 5

SSF (solid-state fermentation) reactors, 313316

Stable RNA species, 121

Staining. See Gram staining.

Standard operating procedures (SOP), 10

Stationary phase, 178179

Stationary phase chromatography, 409

Steady-state method for oxygen removal, 334

Stem cells, 529530

Step feeding/step aeration, biological waste treatment, 556

Steric effects on enzyme immobilization, 98

Sterility, bioreactor scale-up, 329

Sterilization charts, 360361

Sterilizing process fluids. See also Cleaning bioreactors.

continuous sterilization, 361

depth filters, 362363

vs. disinfection, 356

filter sterilization, 361

gases, 362364

glass wool filters, 362

grow-through tests, 363

kinetics of death, 356357

liquids, 357362

probability of extinction, 356

sterilization charts, 360361

surface filters, 362363

Steroid hormone receptors, 139

Sterols, 22

Stirred-tank bioreactors for animal cell cultivation, 447

Stoichiometric calculations

degree of reduction, 230235

elemental balances, 230

Stoichiometry by oxidation-reduction half-reactions, 237240

Stop codons, 125

Stop signals, 121

Storage granules, procaryotes, 20

Streptokinase, uses for, 102

Streptomyces, 477

Strong promoter, 121

Strong terminators, 121

Structural proteins, 30

Structured models, 191

Submerged culture, bioreactor considerations in plant cell cultivation, 467

Submerged tank process, penicillin production, 6

Substrate inhibition, 7679, 195

Substrate-limited growth, 192194

Sucrose, 40

Sulfation, 116

Sulfur, macronutrient, 53

Suppressor mutations, 249

Surface filters, 362363

Surface immobilization, 8790

Surface method of penicillin production, 6

Suspended animal cell cultures, 447

Suspended cells, 311313

Suspension cultures

bioreactor considerations in plant cell cultivation, 462463

in plant cell cultivation, 458459

SYMBA process, 548, 571572

Symbiosis, model of mixed culture interaction, 538

Synonymous mutations, 259

Synthetic biology, 509511

Systems biology, 29, 267, 509511. See also Genomics.

T

T (thymine), 45, 47

TA cloning, 262

Taq (Thermus aquaticus), 14

Taxonomy of cells. See Cell taxonomy.

TCA (Krebs, tricarboxylic acid) cycle, 149152

Teichoic acids, 19

Telomere synthesis, 115

Temperate phages, 256

Temperature activation, 8283

Temperature effects, batch cell growth kinetics, 184185

Temperature inactivation, 83

Termination step, 124125

Tessier equation, 194

Testing for proteins, 264

Tetramers, 487

Thermal denaturation, 83

Thermoacidophiles, 21

Thermodynamic equilibrium and cell death, 51

Thermodynamics of biological reactions, 240242

Thermophiles, 14

Thermus aquaticus (Taq), 14

Three-dimensional printing of living cells, 300

Three-dimensional structure, proteins, 3334

Thylakoids, 24

Thymine (T), 45, 47

Tissue engineering, 519523

TKN (total Kjeldahl nitrogen), 551

TOD (total organic carbon), 550

TOPO cloning, 262

Total Kjeldahl nitrogen (TKN), 551

Total organic carbon (TOD), 550

Totipotency in plant cell cultivation, 457461

Toxic aromatic compounds (biodegradation of xenobiotics), 157158

Transcription terminators, 121

Transcriptomics, 270

Transduction, gene transfer and rearrangement, 254256

Transfection, 265266

Transfer (tRNA), 4950

Transformation, gene transfer and rearrangement, 254

Transformed cells, 435436, 479

Transgenic plants and animals, 482484

Transport proteins, 30

Transport vesicle fusion, 127

Transposons, gene transfer and rearrangement, 257

Tray bioreactors, 314

Trickling biological filters, biological waste treatment, 558561

Tricoplusia ni (cabbage looper), 480

tRNA, 4950, 121

True bacteria (eubacteria)

evolution of, 15

Gram staining, 18

photosynthesis, 19

Trypanosomes, 27

Trypsin, uses for, 102

Tubulin, 25

Turbidity, 172

Turbidostats, 208210

Two-dimensional gel electrophoresis, 270

Two-phase fermentation, 489

Type IIS enzyme, 262263

U

U (uracil), 45

Ubiquitination, 116

Ubiquitins, 116

UCT process for biological waste treatment, 571

UF (ultrafiltration), separation of soluble products, 395398, 403

Ultrasonic vibrators, separation of insoluble products, 383

Unbalanced growth, 191

Uncompetitive inhibitors, enzyme kinetics, 7576

Union Carbide, 552

Units, 70

UNOX process for biological waste treatment, 552, 558

Unselectable mutations, 250

Unstable RNA species, 121

Unsteady-state method for oxygen removal, 333

Unstructured nonsegregated models, 192201

Unwinding enzymes, 117

Uracil (U), 45

USDA Northern Regional Research Laboratory, 56

V

Vacuoles, 24

Vacuum-tray dryers, purification process, 423

van der Waals forces, 63

Variable-volume continuous culture bioreactors. See Fed-batch bioreactors.

VEFCS (very enriched fructose corn syrup) production, 595

Viable cell count, 171

VIP process for biological waste treatment, 571

Viral gene delivery systems, 524

Viral infection, models of, 524527

Virgin zone, separation of soluble products, 405

Viruses. See also HIV (human immunodeficiency) virus; Retroviruses.

capsid coating, 17

classifying, 15

definition, 16

infecting bacteria. See Phages.

lysogenic cycle, 17

lytic cycle, 17

mode of reproduction, 17

size, 16

structure, 1617

that infect bacteria. See Phages.

Vm, interpreting, 7071

Volatile acid formation, biological waste treatment, 564

Volatilized material, biological waste treatment, 551

Volumetric productivities in plant cell cultivation, 468

Volutins in procaryotes, 20

W

Wastes, types of, 549

Wastewater treatment. See also Mixed culture biological waste treatment.

algae for, 27

characteristics, 549551

converting to useful products, 571572

protozoa for, 28

Weak terminators, 121

Western blot testing, 264

Whiskey manufacturing, 546

Wild type mutations, 248

Working volume, bioreactor scale-up, 328

X

Xenobiotics biodegradation (toxic aromatic compounds), 157158

X-press, separation of insoluble products, 384

Y

Yamanaka, Shinaya, 529

Yeast-mediated cloning, 263

Yeasts

definition, 25

in genetic engineering, host-vector systems, 478

reproductive modes, 25

Saccharomyces cerevisiae, 2526

Yield coefficients

maintenance, 227229

oxygen, 227229

theoretical predictions, 235236

Yield factors for aerobic growth, 182

Z

Zwitterion, 32

Zygotes, 23

Zymomonas, 161

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