9780306473494

Biotechnology is a rapidly moving field, which builds on the competence and interplay of many different disciplines; biochemistry, microbiology, molecular biology and chemical engineering. The quantitative treatment of biological processes is today a prerequisite for both the design of new bioprocesses and the analysis of cellular function.The present text is an extensively revised edition of the textbook first published in 1994. The quantitative treatment of bioprocesses is a central theme in this book. The book has been restructured to make it more easily accessible to the reader, the material has been updated and several new topics have been added in the text.The focus is on the bioreactor and the processes that occur in the reactor, i.e. the coupling between the reactions occurring in the cell and its environment. The microbial cellular metabolism is the starting point in the treatment. Tools for the quantitative analysis of cellular functions - macroscopic mass balancing, thermodynamics of microbial processes, metabolic network analysis and kinetic modelling - are gradually introduced. After analysis of the cellular reactor, the interaction between the cell and its environment is treated in chapters concerning mass transfer and design of bioprocesses. Finally, the complex subject of scale-up is presented.The book combines, in a rather unique way, a quantitative treatment of physiology at the cellular level with a treatment of the bioreactor and interaction between the cellular reactor and the bioreactor. Many examples and problems are used to illustrate important concepts in the text.

List of Symbols

xi

Bioreaction Engineering: From Bioprocess Design to Systems Biology

1

(8)

The Structure of the Book

3

(4)

Some Comments on Nomenclature used in the Book

7

(1)

A Final Note

8

(1)

References

8

(1)

From Cellular Function to Industrial Products

9

(38)

Cellular Growth

10

(27)

From Genotype to Phenotype

13

(2)

Transport Processes

15

(1)

Free Diffusion

16

(4)

Facilitated Diffusion

20

(2)

Active Transport

22

(2)

Catabolism

24

(1)

Glycolysis

25

(2)

TCA Cycle and Oxidative Phosphorylation

27

(2)

Fermentative Pathways

29

(1)

Anabolism

30

(5)

Secondary Metabolism

35

(2)

Secreted Proteins

37

(1)

Biotech Processes -- An Overview

37

(10)

Strain Design and Selection

38

(2)

Fermentation Media

40

(1)

Criteria for Design and Optimization

41

(1)

Strain Improvement

42

(3)

References

45

(2)

Biochemical Reactions -- A First Look

47

(48)

The Continuous Stirred Tank Reactor

47

(6)

Yield Coefficients

53

(4)

Black Box Stoichiometries

57

(3)

Degree of Reduction Balances

60

(13)

Systematic Analysis of Black Box Stoichiometries

73

(4)

Identification of Gross Measurement Errors

77

(18)

Problems

88

(4)

References

92

(3)

Thermodynamics of Biochemical Reactions

95

(24)

Chemical Equilibrium and Thermodynamic State Functions

95

(8)

Changes in Free Energy and Enthalpy

97

(5)

Combustion -- A Change in Reference State

102

(1)

Heat of Reaction

103

(6)

Non-equilibrium Thermodynamics

109

(10)

Problems

115

(3)

References

118

(1)

Biochemical Reaction Networks

119

(70)

Basic Concepts

119

(5)

Growth Energetics

124

(18)

Consumption of ATP for Cellular Maintenance

125

(3)

Energetics of Anaerobic Processes

128

(4)

Energetics of Aerobic Processes

132

(10)

Simple Metabolic Networks

142

(9)

Flux Analysis in Large Metabolic Networks

151

(38)

Use of Measurable Rates

153

(10)

Use of Labeled Substrates

163

(8)

Use of Linear Programming

171

(8)

Problems

179

(7)

References

186

(3)

Enzyme Kinetics and Metabolic Control Analysis

189

(46)

Michaelis-Menten and Analogous Enzyme Kinetics

190

(5)

More Complicated Enzyme Kinetics

195

(12)

Variants of Michaelis-Menten Kinetics

195

(6)

Cooperativity and Allosteric Enzymes

201

(6)

Metabolic Control Analysis

207

(28)

Problems

233

(1)

References

234

(1)

Modeling of Growth Kinetics

235

(80)

Model Structure and Complexity

237

(3)

A General Structure for Kinetic Models

240

(5)

Specification of Reaction Stoichiometries

240

(2)

Reaction Rates

242

(2)

Dynamic Mass Balances

244

(1)

Unstructured Growth Kinetics

245

(20)

The Black Box Model

245

(8)

Multiple Reaction Models

253

(8)

The Influence of Temperature and pH

261

(4)

Simple Structured Models

265

(13)

Compartment Models

265

(9)

Cybernetic Models

274

(4)

Mechanistic Models

278

(12)

Genetically Structured Models

279

(10)

Single Cell Models

289

(1)

Morphologically Structured Models

290

(25)

Oscillating Yeast Cultures

295

(5)

Growth of Filamentous Microorganisms

300

(6)

Problems

306

(5)

References

311

(4)

Population Balance Equations

315

(24)

Problems

335

(3)

References

338

(1)

Design of Fermentation Processes

339

(84)

The Stirred Tank Bioreactor

340

(32)

Batch Operation

342

(10)

The Continuous Stirred Tank Reactor

352

(7)

Biomass Recirculation

359

(5)

The Stirred Tank with Substrate Extracted from a Gas Phase

364

(3)

Fed-batch Operation

367

(5)

The Plug Flow Reactor

372

(8)

Dynamic Analysis of Continuous Stirred Tank Bioreactors

380

(43)

Dynamic Response of the Reactor for Simple, Unstructured Kinetic Models

380

(8)

Stability Analysis of a Steady State Solution

388

(9)

Dynamics of the Continuous Stirred Tank for a Mixed Microbial Population

397

(12)

Problems

409

(11)

References

420

(3)

Mass Transfer

423

(54)

Gas-Liquid Mass Transfer

425

(31)

Models for k1

428

(2)

Interfacial Area and Bubble Behavior

430

(8)

Empirical Correlations for k1a

438

(4)

Mass Transfer Correlations Based on Dimensionless Groups

442

(6)

Gas-Liquid Oxygen Transfer

448

(5)

Gas-Liquid Mass Transfer of Components Other than Oxygen

453

(3)

Mass Transfer to and into Solid Particles

456

(21)

External Mass Transfer

456

(4)

Intraparticle Diffusion

460

(9)

Problems

469

(5)

References

474

(3)

Scale-Up of Bioprocesses

477

(42)

Scale-up Phenomena

477

(1)

Bioreactors

478

(4)

Basic Requirements and Reactor Types

478

(2)

The Stirred Tank Bioreactor

480

(2)

Physical Processes of Importance for Scale-Up

482

(26)

Mixing

482

(4)

Power Consumption

486

(5)

Heat Transfer

491

(4)

Scale-Up Related Effects on Mass Transfer

495

(1)

Rheology of Fermentation Broths

496

(5)

Flow in Stirred Tank Reactors

501

(7)

Metabolic Processes Affected by Scale-up

508

(2)

Scale-up in Practice

510

(9)

Problems

514

(3)

References

517

(2)

Index

519

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Bioreaction Engineering Principles

0306473496

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