9-Engineering Protein Evolution

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1、DirectedMolecularEvolutionofProteins:orHowtoImproveEnzymesforBiocatalysis.EditedbySusanneBrakmannandKaiJohnssonCopyrightã2002Wiley-VCHVerlagGmbH&Co.KGaAISBNs:3-527-30423-1(Hardback);3-527-60064-7(Electronic)9EngineeringProteinEvolutionStefanLutzandStephenJ.Benkovic*9.1IntroductionProteinsareinvolve

2、dinvirtuallyeveryaspectofalivingorganism,yettheyarecom-posedofonlytwentynaturalaminoacids.Theprotein'stremendousdiversityorigi-natesfromitsstructuralandfunctionalversatility,achievedthroughpolymerizationofthechemicallydistinctaminoacidbuildingblocksintosequencesofvaryingcomposi-tionandlength.Uponfo

3、ldingintocomplexthree-dimensionalstructures,thesemacromoleculesturnintomolecularmachineswiththeabilitytoaccelerateeventhemostcomplexchemicalreactionsbymanyordersofmagnitudeswithunsur-passedselectivityandspecificity.Thesuperiorperformanceofproteinsinrespecttofunctionaldiversity,specificity,andeffici

4、encyhasattractedscientistsandengineersaliketocreatetailor-madecata-lystsbyproteinengineering.Customizingaproteintowardspracticalapplicationssuchasindustrialcatalysts,biosensors,andtherapeuticsoffersmanyeconomicincen-tives.Atthesametime,proteinengineeringcanaddressfundamentalquestionsofproteindesign

5、inrespecttotheirstructureandfunction.Thiscanthenleadtothedevelopmentofnewtechnologiesfacilitatingthemoredirectedexplorationofproteinsequencespace.AreadilyavailableandabundantresourceforexamplesonhowtoengineerproteinsisNatureitself.Themechanismsofnaturalproteinevolutionhaverepeatedlysuc-ceededinadap

6、tingproteinfunctiontoeverchangingenvironments.Understandingtheprinciplesandmotiveswherebynewproteinstructuresandfunctionsemergecanprovideusefulguidelinesforproteinengineering.Thischapterisdirectedtowardsthemechanismsofnaturalproteinevolution,theirimplicationsonstructureandfunction,andtheirexperimen

7、talimplementationinvitro.1789EngineeringProteinEvolution9.2MechanismsofProteinEvolutioninNatureTwofundamentalapproachescanbeemployedtogeneratenovelproteins;i)thedenovoarrangementofsmall,structuredpeptidesor