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1、CHAPTER6ExamplesofPathwayManipulations:MetabolicEngineeringinPracticeNaturehasprovidedaremarkablearrayofmetabolicpathwaysaswit-nessedbythediversityofextantmicroorganisms.Incertaincases,theassemblyandkineticcoordinationofsuchpathwaysinaparticularorganismaresuitableforausefulcommer
2、cialapplication.Inmostcases,however,geneticimprovementsarerequiredfortheoptimizationoftheconversionreactionsandkineticpropertiesofacelltorenderitsuitableforpracticaluse.Theseimprovementsareguidedbythecurrentunderstandingofmicro-bialmetabolismandmoleculargeneticsandimplementedbymo
3、lecularbiologicaltechniquesandrecombinantDNAtechnology.Therationaltrans-ferofconversionpathwayshasproducednewanddesirablefunctionalitiesincells,thusbenefitingthepharmaceutical,agricultural,food,chemical,andenvironmentalsectors.Inthischapterwereviewapplicationsofmetabolicpathwayma
4、nipulation.WefollowtheclassificationofCameronandTong(1993),slightlymodified,inorganizingthelargenumberofexamplesinbasicallyfivegroups,i.e.,203204MetabolicEngineeringapplicationsaimingat(a)yieldandproductivityimprovementofproductsmadebymicroorganisms,(b)expansionoftherangeofsubsta
5、ncesthatcanbemetabolizedbyanorganism,(c)formationofnewandnovelproducts,(d)generalimprovementofcellularproperties,and(e)xenobioticdegrada-tion.Wehavethreegoalsinreviewingtheseapplicationsinthecontextofthisbook.First,weprovideasampleofthetrulyenormousrangeofpossibilitiesforbiocatal
6、ystimprovementaffordedbypathwaymanipulationandmetabolicengineering.Wenotethatthisreviewisfocused,almostexclusively,onindustrialapplications.Exceptfortheintroduction(Chapter1)andafewpassingreferences,verylittleisincludedonthebroadapplicationsofmetabolicengineeringinthemedicalfield
7、.Thereasonis,simply,thatmostoftheworkinthisfieldiscurrentandnotsufficientlycrystallizedforourreviewpurposes.Reportedprogress,however,leaveslittledoubtabouttheimpactofthetoolsandmethodologiesofmetabolicengi-neeringinanalyzingtissueandorgansinvivoandinvitro,aswellasprovidingfundame
8、ntalsfortherationalanalysisoftheorganiza
