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Bioprocess Engineering

Basic Concepts

Second Edition

PRENTICE HALL PTR INTERNATIONAL SERIES

IN THE PHYSICAL AND

CHEMICAL ENGINEERING SCIENCES

BALZHISER, SAMUELS, AND ELIASSEN Chemical Engineering Thermodynamics

BEQUETTE Process Control: Modeling, Design, and Simulation

BEQUETTE Process Dynamics

BIEGLER, GROSSMAN, AND WESTERBERG Systematic Methods of Chemical Process Design

BROSILOW AND JOSEPH Techniques of Model-based Control

CONSTANTINIDES AND MOSTOUFI Numerical Methods for Chemical Engineers with MATLAB Applications

CROWL AND LOUVAR Chemical Process Safety: Fundamentals with Applications, 2nd edition

CUTLIP AND SHACHAM Problem Solving in Chemical Engineering with Numerical Methods

CUTLIP AND SHACHAM Problem Solving in Chemical and Biochemical Engineering with POLYMATH, Excel, and MATLAB, Second Edition

DENN Process Fluid Mechanics

ELLIOT AND LIRA Introductory Chemical Engineering Thermodynamics

FOGLER Draft Copy of Essentials of Chemical Reaction Engineering

FOGLER Elements of Chemical Reaction Engineering, 4th edition

HIMMELBLAU AND RIGGS Basic Principles and Calculations in Chemical Engineering, 7th edition

HINES AND MADDOX Mass Transfer: Fundamentals and Applications

PRAUSNITZ, LICHTENTHALER, AND DE AZEVEDO Molecular Thermodynamics of Fluid-Phase Equilibria, 3rd edition

PRENTICE Electrochemical Engineering Principles

SHULER AND KARGI Bioprocess Engineering, 2nd edition

STEPHANOPOULOS Chemical Process Control

TESTER AND MODELL Thermodynamics and Its Applications, 3rd edition

TURTON, BAILIE, WHITING, AND SHAEIWITZ Analysis, Synthesis, and Design of Chemical Processes, 3rd edition

VICENTE, NORI, AND FOGLER Solutions Manual for Elements of Chemical Reaction Engineering, Fourth Edition

WILKES Fluid Mechanics for Chemical Engineers, 2nd edition

WILKES Solutions Manual for Fluid Mechanics for Chemical Engineering, 2nd edition, with Microfluidics and CFD

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ISBN 013081908

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For Andy, Kristin, Eric, and Kathy

and for Karen

Contents

vii

PREFACE TO THE SECOND EDITION xvii

PREFACE TO THE FIRST EDITION xix

Part 1 Introduction 1

1 WHAT IS A BIOPROCESS ENGINEER? 1

1.1. Introductory Remarks 1 1.2. Biotechnology and Bioprocess Engineering 2 1.3. Biologists and Engineers Differ in Their Approach to Research 3 1.4. The Story of Penicillin: How Biologists and Engineers Work Together 3 1.5. Bioprocesses: Regulatory Constraints 8 Suggestions for Further Reading 10 Problems 10

Part 2 The Basics of Biology: An Engineer’s Perspective 11

2 AN OVERVIEW OF BIOLOGICAL BASICS 11

2.1 Are All Cells the Same? 11 2.1.1. Microbial Diversity, 11

3.3.3. Experimentally Determining Rate Parameters

Preface to the

Second Edition

xvii

In the decade since the first edition of Bioprocess Engineering: Basic Concepts , biotech- nology has undergone several revolutions. Currently, the ability to sequence the genome of whole organisms presents opportunities that could be hardly envisioned ten years ago. Many other technological advances have occurred that provide bioprocess engineers with new tools to serve society better. However, the principles of bioprocess engineering stated in the first edition remain sound. The goals of this revision are threefold. We want to capture for students the excite- ment created by these advances in biology and biotechnology. We want to inform students about these tools. Most importantly, we want to demonstrate how the principles of bio- process engineering can be applied in concert with these advances. This edition contains a new section in the first chapter alerting students to the regu- latory issues that constrain bioprocess design and modification. We believe students need to be aware of these industrially critical issues. Part 2, “An Overview of Biological Basics,” has been updated throughout and expanded. Greater emphasis is given now to posttranslational processing of proteins, as this is a key issue in choice of bioprocessing strategies to make therapeutic proteins. Basic processes in animal cells are more com- pletely described, since animal cell culture is now an established commercial bioprocess technology. Chapter 5 is made more complete by introduction of a section on noncarbohy- drate metabolism. Key concepts in functional genomics have been added to prepare stu- dents to understand the impact of these emerging ideas and technologies on bioprocesses.

Preface to the

First Edition

xix

Bioprocess engineering is the application of engineering principles to design, develop, and analyze processes using biocatalysts. These processes may result in the formation of desirable compounds or in the destruction of unwanted or hazardous substances. The tools of the engineer, particularly the chemical engineer, will be essential to the successful ex- ploitation of bioprocesses. This book’s main purpose is to introduce the essential concepts of bioprocessing to traditional chemical engineers. No background in biology is assumed. The material in this book has been used as a basis for a course at Cornell University. Although it was designed primarily for seniors and entering graduate students from chemical engineering, students from agricultural engineering, environmental engineering, food science, soil science, microbiology, and biochemistry have successfully completed this course. Parts 1 and 2 outline basic biological concepts. These eight chapters are not in- tended to be a replacement for good courses in microbiology, biochemistry, and genetics. They simply provide sufficient information to make the rest of the book accessible to the reader. A reader who desires a more in-depth understanding of the key biological concepts is referred to the suggested readings at the end of each chapter. Chapters 3 and 6 differ in that they are more detailed and introduce concepts not normally found in the standard bio- logical textbooks. In Part 3, “Engineering Principles for Bioprocesses,” we focus on the generic com- ponents of bioprocessing that do not depend on the type of cell used in the process. In

Part 4 we discuss applications to special systems and the particular characteristics of mixed cultures, genetically engineered cells, plant cells, and animal cells. These applica- tion chapters reinforce the previous engineering and biological concepts while providing more detailed information about important new biological systems. This book reflects useful and important suggestions from many people. Students in Chemical Engineering 643 (“Introduction to Bioprocess Engineering”) at Cornell Univer- sity in Fall 1989 provided written critiques on the chapters. This input has been invaluable and is deeply appreciated. The two external reviewers of this text also provided invaluable suggestions. Harvey Blanch, Charles D. Scott, and Octave Levenspiel have provided one of us (FK) with suggested homework problems, which have greatly enhanced the poten- tial usefulness of this book. Finally, the superb technical skills of Bonnie Sisco have been instrumental in converting nearly incomprehensible written scrawls into a readable text. Finally, both authors wish to thank their families for their patience and support dur- ing this process.

Michael L. Shuler Fikret Kargi

xx Preface to the First Edition