Basic Biotechnology 2 ed

573 Pages·2006·91.61 MB·English

by  Colin Ratledge

BaSK Biotechnology
Biotechnology impinges on everyone-'s lives. It is one oftlle maJor rechnologies
oftbe twenty..first century. les huge, wide-r.mging, multhlisdplinaTY activities
¡nelude recombiIlanr ONA: techniques, doning 3ud geoetics, and the applica
tion ofmicrobiology to the production ofgoods as prosak as bread, beer, cheese
and antibiotics. Jt continue$ tO revolutionise 1:realnlents ofmany diseases, and
is used lo provide clea.n tedlnologie5 and todeal with environmental probJems.
Basic Blo:t'chtwlogyis a textbook. thal gives aJuU accouDtofthecu.rrentstate of
biotechnology, providing!he ~ader with iruight, inspiratlon and instruction.
The fundamental aspects lhat Uflderpin biotechnoiogy are explained through
examples fiom me pbarmaceutical, food and environmental industries. Olap
ters on the public pen::eption ofbiot.echnology and the business aud economics
ofthe subject are <"l150 Included.
The book is esse.Drial reading' fue all students and teachen ofbiotechnology -'
and applied microbiology, and forreseuchers in the many blotl!Chnologyindus
tries.
Basic Biotechnology
SECOND EDITION
eó'ed by
Calin Ratledge and Bj0rn Kristiansen
Univefsiry a(Hul!, UK Europeon Siorechoo/ogists, Norwoy
r
I
www.k-t-dra.com
HCAMBRIDGE
~ UNIVERS.ITY l'RESS
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o
Cambridge University ('ress 2001
Thi¡; bwk is In copyrigbt.SubjecLt e .t.1tulOryeJIccption
iltId to the provtsloru: ohelevant coll&ffi>e li~ns¡ng agreemenlt.
no teproductio!l ofa ny part may (ake place withoul
Ihe writtfn pe~ion ofCambridge Univ=;ity Press.
f'irsl published 2001
Re-prinled2001
Printcd in th/!; Uniled KingdOlIl al the Unil'!'ulty PI"eI'5. Cambridge
ISBN O 52\ no7:/¡ 2 hardba.ck
ISBN O 521 779170 p;lpe1'back
Contents
l.ist 01 c()f)trlburors page xi
""fa" 'v
Part I Fundamenab and principies
Publlc perceptfon ofblotec:hnology JOHN E. SMITl-t 3
1.1 Introductlon 3
1.2 Public il.warenc$S oC genetic engineering 4
1.3 Regulatary requirl!mencs - saretyof ge.netically ellgineered fuods 7
lA Labelling-howfarsho\Jldilgo? 10
1.5 Policy maldng 11
1.6 Areas ofsignificantpublic concem 12
1.7 Condusions 16
1.8 Further reading 16
2 Biochemistry and physiolo¡y 01 crowth and metaboli5m 17
COLlN RATLEDGE
2.1 Introducrion 17
2.2 Metabolisrn 18
2.3 Catabolic pathways 21
,.
2'< Gluconeogenesis 2.
2.5 Energy production in aerobic m.iCJ'OoOrg;¡.nisros
2.6 Anaerobicmetabolism 32
2.7 Biosyntbesis 35
..
2.8 Control of m etabolic processes 38
29 Efficiency of microbial growtb 43
2.10 Further readJng
1 Stoichiometry and kinetics of mlcroblaJ growth from a 45
thermodynamk perspective IIHEIJNEN
Nomendature 45
3.1 lntroduction "
••
3.2 Stoichiometty ca1colations
33 srolchiomell:)l pred.ictions based on Gibbs enl!l"8Y dissipation 52
3.4 Growth kinetics froma tbermodynamic point(lfview 56
3.5 Further readlng "
•
Genome management and anatysis: prokaryotes "
COUN R. HARWOOD and ANIL WIPAT
4.1 lntroduction 59
.4.~. Bactmal chromosomes and natural gene transrer 5.
'.3 What i5 geoeru: eogineering and what is it used fuI'? 65
••
The: bask tool5 ofg enetic engineering
'S Coning vectors and librarie5 76
H Analysis ofg enomeslproteomes 81
.'..7 Analysis ofgeoe expression 83
4.,8 8ngineering genes and optimising productll 87
Production ofheterologous prodUClS 89
4.10 In rllko analysis orbacterial genomes 91
4.11 Purther reading 93
,; -1 CONTENTS
5 Genetlc engineering: yea.st5 and filamentOU5 fungi 95
DA\IlD B. ARa-tER. DONAlD A MACKENZIEand DAVID J. JEENES
Glossary 95
5.1 lnrroduction 97
5.2 Introducing DNA intO fungi (fungal uansformiltion) 100
5.3 Gene c10ning lO'
SA Cene structure.organisation;wd expression 116
5.5 SpedaJ metbodologies 119
5.6 Biotechnological applications offungi 120
5.7 Furtber reading 126
6 Mlcrobial proce!lS kinetics jEN5 NIELSEN 127
Nomendature 127
6.1 lntrodUCtiOD 128
6.2 Kinetic modelling ofcell growth 130
6.3 Mass balances fur ideal bioreilctors 141
6.4 FUj"[her re¡¡diog 14'
7 Bloructor design YUSUF CHISTI and 11URRAY MOO-YOUNG 151
Nomecdature 151
7.1 IntroductioD 152
7:1. Bioreactorconfigurations 153
7.3 BioreactordHign teatures 1,5,8,
704 Desigo for sterile operation
7.5 Photobioreacton 162
7.6 He3t transfer 164
7.7 Shear effects in culture "8
7.8 Purrher readios 171
a Mass transfer HENKJ. NOORMAN 173
Nomeodatlire 173
8.1 Introduction 174
8.2 The man transfur srep! 175
8.3 Mass lransfer equatioru 177
8.<4 Determining the volumerrk In3SS tr.msfercoeffidents 183
8.5 The efl'ect o(scale on mass tr.IQSreT 185
8.6 Further reading 180
9 Downstream processlng In blotechnolosy 18'
RAJNI HATTI·ICAUL and BO MATIIA550N
!U Introductlon 187
9.2 Downstrea.m prol:esslng: a muldstage Oper.ldon 187
9.3 SoHd-liquid separation 188
9.4 Rele;ueofinuaccllularcomponents 193
9.5 ConcMuation ofbiologiciI] products 195
9.6 PulificatiorLbychromatography 204
9.7 PnxIUCI funuuladoll 207
9,8 Monitoring ofdownstream processing 209
9.9 Process integradon 210
9.10 Furtherreading 211
10 Measurement and control A LÜBBERT ancI R. SIMVTlS 213
NomencJature 2'13
10.1 lntroduction 214
CONTENTS I
10.2 StructuJ'e OrpnX"eS5 models 215
10.3 Kinetic Tate expreulons 216
10.4 AdV3nc~ mode.lliugcollliideratiollS 222
10.5 I'rocen supemsion and control "a
10.6 Open·loop control 230
10.7 Closed·Joop control 231
10..8 Condusioo 23.
10.9 FUl1her reading ""
I1 Process economlcs BJ0 RN KRIsnANSENRAJNI 239
tu Introduction 23'
11.2 Tbestartingpoint 240
11.3 Cost e.1:imóltH 240
n.4 Process design 242
11.5 DesigTI exercise. 2 ....
11.6 Cap¡tal costs estimates 247
11.7 Oper.lting cosu estimllte5 247
11.8 The costs case - ro build or not ro build 250
11.9 Further reading 252
Part 11 Practical 8Jlpllcations 253
12 The business 01 blotechnology WILLlAM BAlNS 255
and CHRJS EVAN$
l2.1 Introductlon 255
12.2 What i5 biorechnoloQ' used for? 255
12.3 Biotechnology companies. tbeir care and nurturing 26()
12.4 ln~onent in biotechnology 26S
12.5 WhD needs management? 275
12.6 Patento; and biorechnology 278
12.7 Condusion: jumping the feoce 279
12.8 Punherreading 279
1) Amino acids L EGGEUNG, W PFEFFERLE and H. SAHM 281
13.1 Introduction 281
13.2 CommericaJ l15eofatuinoadds 282
13.3 Prodllction methods and 10015 28'
13.4 L-Glutamate 285
13.5 l-Lyslne 289
13.6 L-1hrronine 2'"
13.7 L·PhenylaJaJ.1ine 296
13.8 L'Tryptophan 29'
13..9 L·AlIpartare 300
13.10 Outlook. 302
13.11 Acknowledgements 302
13.12 Furtherreading 302
14 Organic adds CHRISTIAN P. KUBICEK 305
14.1 lntroduction 305
OO.
14.2 CitrJc add
14.3 Gluconic acid 315
14.4 Lactic acld 317
14..5 Other acids 319
14.6 Furtber reading 32<
viii CONTENTS
15 Microbial polyhydroxyalkanoates.pofytaccharldesand lipids
AUSTAIRJ. ANDERSON andJAMESP.WYNN 325
15.1 Introduction 325
15.2 Microb¡al polyhydroxyalhnoates 325
15.3 Microbial polysaccharides 333
15.4 Microbl.1..llipids 339
15.5 Further readiog 348
16 Antibiotics DAVIDALOWE 349
16.1 Jntroduction 349
16.2 Biosynthesis 351
16.3 5traln improw:ment 351
16.4 Genetic mgineering 35<1
16.5 AnaIysis 354
16.6 Culture preservarlon and aseptic.propagatioo 354
16.7 5cale-up 355
16.8 Fermentadon 356
16.9 hnicillim 361
16.10 Cephalosporins 367
16.11 New fJ-Jactam technologies 368
16.12 Aminoglycoside.s 370
16.13 Macrolides 373
16.14 Economics 373
16.15 Good Ma.nufac[uring Practices 37'
16.16 Furtherreading 375
17 Baker's yeast SVEN·OLOF ENfORS 377
Nomenclature 377
17.1 lntroduction 378
17.1 Mediurnforbaker'syeastproduction 380
17.3 Aerobicethanol formationandconsumption 381
17.4 Ihe fed-batch technique used ro control ethanoJ proc:luction 384
17.5 Industrial process control 386
17.6 PrOCe5S outline 387
17.7 Furtberre<Lding 389
18 Production of enqmes DAVID A LOWE 391
18.1 Introduction 391
18.2 Enzymes from <Lnimaland plant sourccs 393
18.3 Enzymes from microbial sources 395
13.4 Large-sca]e productlon 396
18.5 Biochemical fundamentals 39'
18.6 Genetic e.ngineering 400
18.7 Recovery ofe nzymes 40'
18.8 lrolatlon ofsoluble enzymes 403
18.9 Enzyme purificarlon '0'
18.10 (mmobiliscd enzymes 40.
18.11 Legislative aod safety aspecu 407
18.12 Further reading 408
19 Synthesis of chemlcals ll5lnl cnzymes
THORL8F ANTHONSEN
19.1 Introduction 409
19.2 Hydrolytic enzymes .12
CONTENTS be
<1,
19.3 CJ¡jr;¡J building blocl3 for synthesis
19.4 Reductions and oxidCLtiOns 419
19.5 Use of enzymes in sugar chemistry 422
19.6 Use ofenzymes to make aminoacids and peptides 426
19.7 Further reading 428
10 Recombinant proteins o( high value GEORG-B. KRESSE 429
20.1 Applications ofhigh-value proteins 429
20.2 Analytical enzymes 430
20.3 Therapeutic protei..n.s 436
20.4 Regulatory a.spectS aftherapeutic proteiru: 446
20.5 Outlook to the future ofprotein therapies 446
20,6 Funherread!ng 447
21 Mammallan cen culture N. VRJEZEN. J. P. VAN DIJKEN 449
"'" L HAGGSTROM
21.1 lntroductioll 449
21.2 Mammalian teU Ilnes and their characteristia 4SO
21.3 COInmerical products 452
21.4 Proteinglycosyliltion 453
21.S Media fot [he cultivation ofmammalian cells 'SS
21.6 Mel.4lbolism 458
21.7 Large-scale cultivatíon ofmammalian cells 46'
21.8 Genetic engineerlng ofmammalian (!!lis 468
21.9 Further readiu.g 470
22 Blotransformatlons JOAQU1M M.S. CABRAl ' 7J
22.1 lntrodunion '71
22.2 Biocatalyst selection 473
22.3 Bioca.talyst irnmobilisatioll and performancr 475
22.4 [mmobilised enzyme reactDrs '"
22.5 Bioca.talysis in non<onventiunaJ media '91
22.6 Concluding remaro 500
22.7 Funher re¡¡,ding SOl
2J Immunochemic::al applications M1KE CLARK S03
Glossary 503
23.1 lntroduction 506
23.2 Ann'body S!:n.lcture :md functions 506
23.3 Antibody prorein fragments 510
23.4 Autibodyaffinity 512
23.5 Antibody spec:i.ficity 513
2.3.6 lmmu.nlsation and productioo ofpol~onal :rntisen SI.
23.7 Monoclonal antibodies 517
23.8 Anrlbodyengineecing 518
23.9 Combinatorial and phage display librarles 520
:D.IO In vUm uses ofrecombioant3nd monoclODaJ antibodies 522
23_11 rn viw usesofrecombiuant and mOnodonal antibodies 526
23.l2 Furrher read.ing 529
14 Environmental applications PHIUPPE VANDEVIVERE S31
and Wll1.Y VERSTRAETE
24..1 lntroduction 531
24. . 2 Tteatment ofwaste water 532
)( CONTENTS
24.3 Digestion of org;¡.nicslunies 540
24.4 TreallIlent ofsolid wastes 54'
24,S Treatmen! ofwastegases 545
24.6 Soil rcmediiltion 549
24.7 Treatmenlofgl'oundwarer 554
24.8 Furtherreading 557
1""'" 559