title author publisher isbn10 | asin print isbni3 ebook isbn13 Tanguage subject publication date ee ade subject Biochemical Engineering Blanch, Harvey W. (0824789490 9780824789497 9780585157412Pagei Biochemical Engineering Harvey W. Blanch Douglas S. Clark University of California at Berkeley Berkeley, California Marcet Deke, Inc New York + Bast » Hono Konc page iPage ti Library of Congress Cataloging-in-Publication Data Blanch, Harvey W. Biochemical engineering / by Harvey W. Blanch, Douglas S. Clark. p.cm. Includes index. ISBN 0-8247-8949-0 (alk. paper: hardcover) 1. Biochemical engineering. I. Clark, Douglas S. IL Title. TP248.3.B625 1996 6607.63de20 95-37549 cr ‘The publisher offers discounts on this book when ordered in bulk quantities. For more information, write to Special Sales/Professional Marketing at the address below. This book is printed on acid-free paper. Copyright © 1996 by MARCEL DEKKER, INC. All Rights Reserved Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher. MARCEL DEKKER, INC. 270 Madison Avenue, New York, New York 10016 Current printing (last digit) 10987654 PRINTED IN THE UNITED STATES OF AMERICA page_iiPage i Preface Biochemical engineering embraces aspects of biochemistry, cell and molecular biology, bioorganic and bioinorganie chemistry, and has at its core the discipline of chemical engineering. Biochemical engineering may be loosely defined as the use of living organisms, or part of them (for example, enzymes), fir the production of chemical or biological materials or the development of new processes. In this sense, the practice of biochemical engineering has a long history, including such early applications as the fermentation of grapes for wine, brewing of beer, cheese manufacture, leavening of bread, and effluent disposal. In mote recent times, biochemiical engineers have been involved in antibiotic fermentations, production of industrial solvents, organic acids. vaccines, blood and tissue products, animal feedstuffs, commercial enzymies and in the treatment of effluents and wastes. ‘The advent of recomlbinant INA and hybridoma teclhnology in the late 1970s opened new avenues for the production of enzymes and therapeutic proteins, and the modification of metabolic pathways for the production of biochemnicals. Today, biochemical engineers work with a variety of cells from microbial, mammalian and plant sources, in the form of single cells and as tissues. Many issues that were vitally important earlier have been resolved in the past decades; these include sterile air filtration, medium and equipment sterilization, aseptic equipment design, and instrumientation. Our knowledge of inicrobial and cellular physiology has expanded rapidly, together with our understanding of enzyme structure and catalytic function, New biological catalysts, such as ribozymes, catalytic antibodies, and modified enzymes provide new tools for the production of chemicals, biochemicals, materials, and therapeutic agents. Exploitation of advances in recombinant DNA technology relies on early studies of | microbial physiology, scale-up and reactordesign, heat and mass transfer in fermentations, and on separation and purification processes, ‘One of the most important tools in biochemical engineering has been continuous culture (the cchemostat); it provided a technique to study microbial physiology under well-defined conditions means to develop kinetic models of microbial growth and, and a page iliPage iv product formation. The theoretical and experimental basis of chemostat operation was originally proposed by Monod! and Novik and Szilard? and it was extensively developed by researchers atthe Microbiological Research Establishment at Porton Downs (U.K.) Sand at the Institute of Microbiology of the Czechoslovak Academy of Sciences‘. The annual review of publications on continuous culture, appearing in Folia Microbiologia’, included developments inthe theory of continuous cultivation, ‘microbial physiology and product formation and applications of the method. In the past twenty years, the number of publications involving chemostats has grown tremendously. Continuous culture has played an important role in understanding the stability of plasmids in recombinant cels, in following ‘events in the cell cycle, and in understanding monoclonal antibody production by hybridoma cells Paralleling these advances in fermentation, the area of separation and recovery of biological products has seen the development of techniques such as ion exchange, affinity and gel permeation ‘chromatography, electrophoresis, aqueous two-phase extraction, and membrane separation processes, Most of these techniques rely on newly-developed materials with suitable properties. The high purity requirement of recombinant proteins has been a significant factor in developing highly-efficient small-scale separation processes. The theoretical underpinnings of these separation processes are based. on biophysical chemistry, colloidal and interfacial phenomena and mass transfer. Appropriate descriptions of intermolecular interactions are important in understanding processes such as precipitation, crystallization, extraction and interactions of biological materials with surfaces, ere have been several fexts that have had a profound influence on the development of biochemical engineering. One of the first texts, writen from a chemical engineering perspective, is F.C. Webb's, book, "Biochemical Engineering”, developed from courses at University College, London®. It ‘emphasizes physical chemistry, kineties, and heat and mass transfer. The first texto integrate irobiology. enzymology and bioprocess enginecring was Aiba, Humphrey and Millis’ "Biochemical Engineering"? It served as the standard reference for many years and provided a valuable introduction to biochemistry and biology for chemiical engineers. Bailey and Ollis’lext "Biochemical Engineering (1) Monod, J, Anal Inst, Pasteur 79, 390 (1980) (2) Novick, A. and L. Srila, Seienee, 112.718 (1950) (9) Herber,D. llsworth, Rand RC. ted. Gen, Microbiol, 1,601 (1956) (4) Mate, I, Beran K, and 7. Fend, Theotetial and Methodological Basis of Continuous Ci Microorganisms, Publishing House of Czech. Academy of Sciences, Prag (1966) (5) Malek 1 and 2. Fend, Folia Microbiologia, 6, 142 (1961) and annual reviews thereafter (6) Webb, PC. Biochemical Engineering, van Nostrand (1964) () Aiba, 8, Harp ax! 2ad edition (1973) ‘A. and NP Millis, Biochemical Enginering, Academic Pres, Ist edition (1964) page iPage Fundamentals"® incorporated modern biology and included sections on the commercial applications of biochemical engineering. It provided students with sufficient background in the life sciences to enable them to address problems in microbial growth, enzyme kinetics an(I metabolic control. This book is a comprehensive textbook of modern biochemical engineering, intended for students in engineering and applied science. With the increasing emphasis on life sciences in engineering curricula, many students interested in biochemical engineering alrea(ly have backgrounds in biochemistry or cell biology. This text therefore (loes not include sections on biochemistry, infictobiology, and molecular and cell biology. There are a number of excellent texts available that can be used as.a supplement to this text, permitting the student to cover biology to any depth required? Material is presented at levels appropriate for both undergraduate and graduate courses in biochemical engineering, and sample course outlines are provided below for courses taken by students with and ‘without backgrounds in the life sciences. Each major topic follows a logical progression from basic principles to more advanced concepts. The major topics include enzyme kinetics and biocatalysis, ‘microbial growth and product formation, bioreactor design, transport in bioreactors, bioproduct recovery, and bioprocess economics and design. Problems are included at the end of each chapter, ranging from straightforward exercises testing knowledge of fundamental concepts to miore complex problems dealing with real systems and real bioprocesses. Although the primary aim of the book isto serve as an instructional text for students of biochemical engineering, it should also be useful to practicing biochemical engineers who are concerned with the basic concepts underlying the design and behavior of bioprocesses. Acknowledgments We are very grateful to Peter Michels and Jeanne George for reviewing preliminary versions of each chapter. Their critical comments on content and presentation were extremely useful. Suggestions offered by teaching assistants and students as the text progressed to the classroom were also invaluable, especially those of Andrew Shuler, M. Scott Clarke, and Marea Frost. Thoughtful and useful reviews of selected chapters were furnished by Jonathan Dordick, Charles Goochee, and Timothy Oolman. Thanks are also owed to Lary Erikson, Doug Lauffenburger, and Jay Bailey for generously supplying several homework problems. We are especially grateful to John Martens for his assistance with the illustrations throughout the text. HARVEY W. BLANCH DOUGLAS S. CLARK (8) Bailey, LE-and D.F. Olis, Biochemical Engineering Fundamentals, MeGraw Hill, Ist edition (1977) and 2nd edition (1986) (9) Suyer: L., Biochemistry, W.H. Freeman, N-Y., th edition (1995); Glazer. ALN, and H. Nikaido, Microhial Biotechnology, W.H. Freeman & Co, (1995) pagev