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Bioprocess Engineering. Kinetics, Sustainability, and Reactor Design PDF

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BIOPROCESS ENGINEERING BIOPROCESS ENGINEERING Kinetics, Sustainability, and Reactor Design SECOND EDITION S L HIJIE IU SunyEsf DepartmentofPaperandBioprocessEngineering, Syracuse,NY,USA AMSTERDAM (cid:129) BOSTON (cid:129) HEIDELBERG (cid:129) LONDON (cid:129) NEW YORK (cid:129) OXFORD PARIS (cid:129) SAN DIEGO (cid:129) SAN FRANCISCO (cid:129) SINGAPORE (cid:129) SYDNEY (cid:129) TOKYO Elsevier Radarweg29,POBox211,1000AEAmsterdam,Netherlands TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UnitedKingdom 50HampshireStreet,5thFloor,Cambridge,MA02139,UnitedStates #2017,2013ElsevierB.V.Allrightsreserved. Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronic ormechanical,includingphotocopying,recording,oranyinformationstorageandretrievalsystem, withoutpermissioninwritingfromthepublisher.Detailsonhowtoseekpermission,further informationaboutthePublisher’spermissionspoliciesandourarrangementswithorganizations suchastheCopyrightClearanceCenterandtheCopyrightLicensingAgency,canbefoundatour website:www.elsevier.com/permissions. Thisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythe Publisher(otherthanasmaybenotedherein). Notices Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchandexperience broadenourunderstanding,changesinresearchmethods,professionalpractices,ormedical treatmentmaybecomenecessary. Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgein evaluatingandusinganyinformation,methods,compounds,orexperimentsdescribedherein. Inusingsuchinformationormethodstheyshouldbemindfuloftheirownsafetyandthesafety ofothers,includingpartiesforwhomtheyhaveaprofessionalresponsibility. Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors, assumeanyliabilityforanyinjuryand/ordamagetopersonsorpropertyasamatterofproducts liability,negligenceorotherwise,orfromanyuseoroperationofanymethods,products,instructions, orideascontainedinthematerialherein. BritishLibraryCataloguing-in-PublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress ISBN:978-0-444-63783-3 ForinformationonallElsevierpublications visitourwebsiteathttps://www.elsevier.com/ Publisher:JohnFedor AcquisitionEditor:KostasMarinakis EditorialProjectManager:ChristineMcElvenny ProductionProjectManager:AnithaSivaraj CoverDesigner:MarkRogers TypesetbySPiGlobal,India Preface to the Second Edition The success of the first edition as an un- Another merge is seen in Chapter 12 on dergraduateandgraduatetextonbioprocess cell cultivation. This chapter now replaces engineering has led to the further develop- the chapter on continuous cultivation in the ment in treaties on reactor analysis and en- first edition and discusses all of the cultiva- zyme kinetics. tion methods: batch, continuous, and fed With the goal of making this text as suit- batch.Thisrearrangementleadstotheelim- ableas the first text on bioprocessengineer- ination of the Chapter on fed-batch cultiva- ing, there were many aspects of chemical tion from the first edition. kinetics,microbiologyorbiochemistry,reac- The major changes to this second edition tion engineering, and bioreaction engineer- include more thorough discussions on the ing that needed to be integrated. The validation of the Monod equation in Chap- second edition furthers this goal, and we ters 9 and 11, and enzymes with complex now have an integrated text on bioprocess structures or with multiple active centers in engineering. We do not make a particular Chapters 7 and 10. While the Monod equa- distinction in the treatment of chemical tion is empirical, its theoretical foundations transformations or bio-transformations. An have now been provided in the text. En- attempt is made to unify the terminologies zymeswithmultipleactivecenterscanbein- in the different fields and bring them into teractive, as ligand binding can alter the bioprocessengineering. enzyme structure, affecting further binding As with the first edition, the straight-line and/or reactivity, and therefore, producing plots for reaction rates, or elaborate ways desiredregulations.Becauseofthedevelop- to render reaction rates to straight lines, are mentsonthetreatiseontheseinteractiveen- missing from this text. The kinetic paramet- zymes, Chapter 7 (which was Chapter 8 in ricestimation(formerlyChapter7inthefirst thefirstedition)onenzymeshasbeenrewrit- edition) is now combined into Chapter 6 on ten; and a new chapter on interactive en- chemical kinetics. It is my hope that the fu- zymes and regulations (Chapter 10) has turegenerationsofbioprocessengineerswill also been written. Another addition to the notrelyonstraight-lineinterpretations.This second edition is Chapter 18: Combustion, text promotes a mechanistic understanding ReactiveHazard,andBioprocessSafety.Re- of the bio-transformations and regulations activehazardandprocesssafetyisbecoming overtheartificial,straight-lineexplanations. arequiredcomponentinourundergraduate Speakingofstraightlinesandgraphicso- education.Thischapterprovidesameansto lutions, the “pinch line” method is now in- include the topic in the undergraduate troduced starting in Chapter 4 on batch curriculum. reactoranalysis.Itprovidesameansforsolv- Ihopeyouwillenjoythissecondedition. ingabatchreactor problem whenthekinet- ics isnot fully understood. Shijie Liu ix Preface to the First Edition All I know is justwhat I read inthe papers. discipline,itevolvedfromaninterdisciplin- Will Rogers arysubjectareaofBiologyandChemicalEn- gineering, to a discipline that covers the Thequoteaboveisquiteintriguingtome, engineering, and engineering science, as- andisreflectiveofthistext.Everythinginthis pects of biotechnology, green chemistry, text can be found either directly, or through and biomass or renewable resource engi- “extrapolation” or “deduction” using the neering. As such, textbooks in this area are books and papers one can find to date. The needed to cover the educational needs of most influential books at this time include the new generation of fine bioprocess engi- “Biochemical Engineering Fundamentals” neers, and not just converting well-versed by J.E. Bailey and D.F. Ollis; “Elements of chemical engineers and engineering-savvy Chemical Reaction Engineering” by H.S. biologists into bioprocess engineers. I hope Fogler; “The Engineering of Chemical Reac- thatthistextbookcanfillthisgap,andbring tions” by L.D. Schmidt; “Chemical Reaction about the maturity of bioprocess engineer- Engineering” by O. Levenspiel; “Bioprocess ing. Yet, some of the materials in this text Engineering-Basic Concepts” by M.L. Shuler aredeepinanalysesthataresuitedforgrad- and F. Kargi; and many others. All of these uate work and/orfor research reference. texts, as well as others, have helped form a Thekeyaspectthatmakesbioprocessen- partofthistext.Itisnotintendedforthistext gineeringspecial isthat it,as adiscipline,is to replace all these great textbooks. This is centeredonsolvingproblemsoftransforma- a mere rearrangement and/or compilation tion stemming from cellular functions, and andismadetogiveyou,thereader,anopp- biological and/or chemical conversions ortunity to understand some of the basic concerningthesustainableuseofrenewable principlesofchemicalandbiologicaltransfor- biomass. The mechanism, rate, dynamic be- mationsinbioprocessengineering. havior, transformation performance, and The computer age has truly revolution- manipulations of bioprocess systems are izedtheliteratureonbioprocessengineering, themaintopics of this text. wellbeyondtheliteraturerevolution,which Chapter1isanintroductiontobioprocess was brought about by the mass production, engineering profession including green oravailability,ofpaperandthedistribution chemistry, sustainability considerations, of books via libraries. The explosion in the and regulatory constraints. Chapter 2 is an shearamountofliteratureandthebirthofin- overviewof biological basics orcellchemis- terdisciplinary disciplines, or subject areas, try including cells, viruses, stem cell, amino in the past decades have been phenomenal. acids, proteins, carbohydrates, and various Bioprocessengineeringisbornofbiotechnol- biomass components, and fermentation me- ogyandchemicalengineering.Withthema- dia.InChapter3,asurveyofchemicalreac- turing of bioprocess engineering as a tion analysis is introduced. The basic xi xii PREFACETOTHEFIRSTEDITION knowledge of reaction rates, conversion, reactions and Langmuir-Hinshelwood- yield, stoichiometry, and energy regularity Hougen-Watson (LHHW) for solid catalysis, for bioreactions are reviewed. The concepts is demonstrated. The applicability of these of approximate and coupled reactions simple kinetic relations is discussed. In areintroduced,providingthebasisofunder- Chapter 9, you will learn both ideal and standing for the metabolic pathway repre- nonideal adsorption kinetics and adsorption sentations later in this book. Mass and isotherms.Ismultilayeradsorptionthetrade- energybalancesforreactoranalyses,aswell markforphysisorption?In9.5,theheteroge- as the definitions of ideal reactorsand com- neous kinetic analysis theory is applied to monlyknownbioreactorsareintroducedbe- reactions involving woody biomass, where fore an introduction to reactor system thesolidphaseisnotcatalytic.Chapter10dis- analyses. Biological and chemical reaction cussescellulargeneticsandmetabolism.The basicsarefollowedbyreactoranalysisbasics replication of genetic information, protein inChapters4and5,includingtheeffectofre- production,substrateuptake,andmajormet- actionkinetics,flowcontactpatterns,andre- abolicpathwaysarediscussed,hintingatthe actor system optimizations. Gasification (of application of kinetic theory in complicated coal and biomass) is also introduced in systems. In Chapter 11 you will learn how Chapter 5. How the ideal reactors are se- cells grow: cellular material quantifications, lected,whatflowreactortochoose,andwhat batch growth patterns, cell maintenance and feed strategies to use are also covered in endogenous needs, medium and environ- Chapter 5. mentalconditions,andkineticmodels.Reac- Chapters6,7,8,9,10,and11arestudiesin tor analyses are also presented in Chapters bioprocess kinetics. In Chapter 6 you will 8and11. learnthecollisiontheoryforreactionkinetics InChapters12and13wediscusscontrolled andapproximationscommonlyemployedto cellcultivation.Continuouscultureandwaste- arrive at simple reaction-rate relations. watertreatmentsarediscussedinChapter12. Kinetics of acid hydrolysis, as an important Exponentialgrowthisrealizedincontinuous unit operation in biomass conversion, is culturing. An emphasis is placed on reactor introduced as a case study. In Chapter 7, performance analyses, mostly using the we discuss the techniques for estimating Monodgrowthmodelintheexamplesinboth kinetic parameters from experimental data, Chapters. Chapter 13 introduces fed-batch breakingawayfromthetraditionalstraight- operations and their analyses. Fed-batch can line approaches developed before the mimic exponential growth in a controlled computer age. You can learn how to use manner,asopposedtobatchoperationswhere modern tools for extracting kinetic parame- no control on growth is asserted besides ters reliably and quickly, without complex environmentalconditions. manipulations of the data. In Chapters Chapter 14 discusses evolution and ge- 8and9,wediscusstheapplicationofkinetic netic engineering, with an emphasis on bio- theory to catalytic systems. Enzymes, enzy- technological applications. You will learn matic reactions, and the application of en- how cells transform, how cells are manipu- zymes are examined in Chapter 8; while lated, and what some of the applications adsorption and solid catalysisarediscussed for cellular transformationandrecombinant in Chapter 9. The derivation of simplified cellsare.Chapter15introducesperspectives reaction-rate relations, such as the on sustainability. Bioprocess engineering Michaelis-Menten equation for enzymatic principles are applied in order to examine xiii PREFACETOTHEFIRSTEDITION the sustainability of biomass economy and previous set-point after a minor disturbance atmospheric CO . Chapter 16 discusses the isanexpectation.InChapter 17, theeffectof 2 stability of catalysts including the activity themasstransferonthereactorperformance, of a chemical catalyst, the genetic stability in particular with biocatalysis, is discussed. ofcellsandmixedcultures,aswellasthesta- Both external mass transfers, eg suspended bility of reactor systems. Sustainability and media; and internal mass transfers, eg the stability of bioprocess operations are immobilizedsystems;aswellastemperature discussed. A stable process is sustainable. effects are discussed. Detailed numerical Multiple steady states, the approach toward solutions can be avoided, or greatly simpli- asteadystate,theconditionsforstableoper- fied, by directly following the examples. ations,andpredator-preyinteractionsarealso Chapter 18 discusses reactor design and discussed. Continuous culture is challenged operation.Reactorselection,mixingschemes, by stability of cell biomass. In ecological ap- scale-up,and sterilizationandaseptic opera- plications,sustainabilityofabioprocessisde- tionsarealsodiscussed. sirable.Forindustrialapplications,theability of the bioprocess system to return to the Shijie Liu Acronyms, Abbreviations, and Symbols a catalystactivity a specificsurfaceorinterfacialarea,m2/m3 a thermodynamicactivity a cumulativeaffinitychangefactor a dimensionlessdispersioncoefficient d a constant A chemicalspecies A adenine A constant A heattransferarea,m2 Ac acetyl ADP adenosinediphosphate AMP adenosinemonophosphate ATP adenosinetriphosphate B chemicalspecies B constant BOD biologicaloxygendemand BOD biologicaloxygendemandmeasuredfor5days 5 B S boundspeciesSonn-sitedenzyme n c constant C chemicalspecies C concentration,mol/Lorkg/m3 C constant C cytosine C dimerformedbyswappingcarboxylicacidtermini D C heatcapacity,J/(molK),orkJ/(kgK) P CoA coenzymeA CHO ChineseHamsterOvarycell COD chemicaloxygendemand CSTR continuouslystirredtankreactor d diameter,m D diameter,m D diffusivity,m2/s D dilutionrate,s(cid:1)1 D dimer D- chiralityoropticalisomers:right-handruleapplies DNA deoxyribonucleicacid DO concentrationofdissolvedoxygen,g/L xv xvi ACRONYMS,ABBREVIATIONS,ANDSYMBOLS DP degreeofpolymerization DS domainswapped e electron E enzyme E energy,kJ/mol E enzymehavingn-subunits n E polymorphmemberorthej-thenzymehavingn-subunits j n EMP Embden-Meyerhof-Parnas f fractionalconversion f fanningfrictionfactor F flowrate,kg/sorkmol/s F Faradyconstant FAD flavinadeninedinucleotideinoxidizedform FADH flavinadeninedinucleotideinreducedform FDA FoodandDrugAdministration FES fastequilibriumstep(hypothesis) g gravitationalacceleration,9.80665m2/s G Gibbsfreeenergy,kJ/mol G Guanine GRAS generallyregardedassafe GMP goodmanufacturepractice GTP guanosinetriphosphate h heightorlength H enthalpy,kJ/molorkJ/kg H harvestingcost C HMP hexosemonophosphate(pathway) Ig immunoglobulin J totaltransferflux,kmol/sorkg/s J transferflux,kmol/(m2s)orkg/(m2s) k kineticrateconstant k masstransfercoefficient,m/s K thermodynamicequilibriumconstant K saturationconstant,mol/Lorkg/L K enzymebindingsaturationconstant,mol/L K overallmasstransfercoefficient(fromgastoliquid) L L length L- chiralityoropticalisomers:lefthandruleapplies m amountofmass,kg m_: massflowrate,kg/s m maintenancecoefficient S M molecularweight,Darton(D)orkg/kmol MC molar(ormass)consumptionrate MG massgenerationrate MR massremovalrate MS molarormasssupplyrate MSS multiplesteadystate n totalmattersinnumberofmoles N masstransferrate,kJ/(m2s)orkg/(m2s) xvii ACRONYMS,ABBREVIATIONS,ANDSYMBOLS N numberofspecies N dimerformedbyswappingaminetermini D NAD nicotinamideadeninedinucleotide NADP nicotinamideadeninedinucleotidephosphate O orderofreaction R OTR oxygentransferrate OUR oxygenutilizationrate p pressure p polymorphenzymeparameter e P probability P pressure P product,orproductconcentration,kg/m3,org/L,ormol/L P power(ofstirrerinput) P productivityorproductionrateofbiomass X P probabilityofthevanishingoftheentirepopulation 0 P probabilityoftheentirepopulationnotvanishing 1 PCR polymerasechainreaction PEP phosphoenolpyruvate PFR plugflowreactor PP pentosephosphate(pathway) PSSH pseudosteadystatehypothesis P/O ATPformationperoxygenconsumption q Thermalflux,J/sorW Q volumetricflowrate,m3/s _: Q thermalenergytransferrateintothesystem r radialdirection r rateofreaction,mol/(m3s)orkg/(Ls) R correlationcoefficient R idealgasconstant,8.314J/(molK) R product,orproductconcentration R recycleratio Re Reynoldsnumber RNA ribonucleicacid s selectivity S entropy S overallselectivity S substrate(orreactant) S substrateconcentration,g/L S surfacearea,m2 Sh Sherwoodnumber SMG specificmassgenerationrate SMR specificmassremovalrate t time,s T temperature,K T thymine TCA tricarboxylicacid u superficialvelocity,m/s U averagevelocityorvolumetricflux

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