Andrianantoandro-2006-Synthetic biology_ n

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REVIEW

Syntheticbiology:newengineeringrulesfor

anemergingdiscipline

ErnestoAndrianantoandro1,3,SubhayuBasu1,3,

DavidKKarig1,3andRonWeiss1,2,*

1DepartmentofElectricalEngineering,PrincetonUniversity,Princeton,NJ,USAand2DepartmentofMolecularBiology,PrincetonUniversity,Princeton,NJ,USA*Correspondingauthor.DepartmentofElectricalEngineering,PrincetonUniversity,J-319,E-Quad,Princeton,NJ08544,USA.E–mail:rweiss@princeton.edu3Theseauthorscontributedequallytothiswork

Received2.2.06;accepted17.3.06

Syntheticbiologistsengineercomplexartificialbiological

systemstoinvestigatenaturalbiologicalphenomenaand

foravarietyofapplications.Weoutlinethebasicfeaturesof

syntheticbiologyasanewengineeringdiscipline,covering

examplesfromthelatestliteratureandreflectingonthe

featuresthatmakeituniqueamongallotherexisting

engineeringfields.Wediscussmethodsfordesigningand

constructingengineeredcellswithnovelfunctionsina

frameworkofanabstracthierarchyofbiologicaldevices,

modules,cells,andmulticellularsystems.Theclassical

engineeringstrategiesofstandardization,decoupling,and

abstractionwillhavetobeextendedtotakeintoaccountthe

inherentcharacteristicsofbiologicaldevicesandmodules.

Toachievepredictabilityandreliability,strategiesfor

engineeringbiologymustincludethenotionofcellular

contextinthefunctionaldefinitionofdevicesandmodules,

userationalredesignanddirectedevolutionforsystem

optimization,andfocusonaccomplishingtasksusing

cellpopulationsratherthanindividualcells.Thediscus-

sionbringstolightissuesattheheartofdesigning

complexlivingsystemsandprovidesatrajectoryforfuture

development.

MolecularSystemsBiology16May2006;

doi:10.1038/msb4100073

SubjectCategories:syntheticbiology

Keywords:contextdependence;engineeringbiology;

multicellularsystem;syntheticbiology

Introduction

Syntheticbiologywillrevolutionizehowweconceptualizeand

approachtheengineeringofbiologicalsystems.Thevisionand

applicationsofthisemergingfieldwillinfluencemanyother

scientificandengineeringdisciplines,aswellasaffectvarious

aspectsofdailylifeandsociety.Inthisreview,wediscussand

analyzetherecentadvancesinsyntheticbiologytowards

engineeringcomplexlivingsystemsthroughnovelassembliesofbiologicalmolecules.Thediscoveryofmathematicallogicin

generegulationinthe1960s(e.g.thelacoperon;Monodand

Jacob,1961)andearlyachievementsingeneticengineering

thattookplaceinthe1970s,suchasrecombinantDNA

technology,pavedthewayfortoday’ssyntheticbiology.

Syntheticbiologyextendsthespiritofgeneticengineeringto

focusonwholesystemsofgenesandgeneproducts.Thefocus

onsystemsasopposedtoindividualgenesorpathwaysis

sharedbythecontemporaneousdisciplineofsystemsbiology,

whichanalyzesbiologicalorganismsintheirentirety.Syn-

theticbiologistsdesignandconstructcomplexartificial

biologicalsystemsusingmanyinsightsdiscoveredbysystems

biologistsandsharetheirholisticperspective.

Thegoalofsyntheticbiologyistoextendormodifythe

behavioroforganismsandengineerthemtoperformnew

tasks.Oneusefulanalogytoconceptualizeboththegoaland

methodsofsyntheticbiologyisthecomputerengineering

hierarchy(Figure1).Withinthehierarchy,everyconstituent

partisembeddedinamorecomplexsystemthatprovides

itscontext.Designofnewbehavioroccurswiththetopof

thehierarchyinmindbutisimplementedbottom-up.At

thebottomofthehierarchyareDNA,RNA,proteins,and

metabolites(includinglipidsandcarbohydrates,aminoacids,

andnucleotides),analogoustothephysicallayeroftransis-

tors,capacitors,andresistorsincomputerengineering.The

nextlayer,thedevicelayer,comprisesbiochemicalreactions

thatregulatetheflowofinformationandmanipulatephysical

processes,equivalenttoengineeredlogicgatesthat

performcomputationsinacomputer.Atthemodulelayer,

thesyntheticbiologistusesadiverselibraryofbiological

devicestoassemblecomplexpathwaysthatfunctionlike

integratedcircuits.Theconnectionofthesemodulestoeach

otherandtheirintegrationintohostcellsallowsthesynthetic

biologisttoextendormodifythebehaviorofcellsina

programmaticfashion.Althoughindependentlyoperating

engineeredcellscanperformtasksofvaryingcomplexity,

moresophisticatedcoordinatedtasksarepossiblewith

populationsofcommunicatingcells,muchlikethecasewith

computernetworks.

Itisusefultoapplymanyexistingstandardsforengineering

fromwell-establishedfields,includingsoftwareandelectrical

engineering,mechanicalengineering,andcivilengineering,to

syntheticbiology.Methodsandcriteriasuchasstandardiza-

tion,abstraction,modularity,predictability,reliability,and

uniformitygreatlyincreasethespeedandtractabilityof

design.However,caremustbetakenindirectlyadopting

acceptedmethodsandcriteriatotheengineeringofbiology.

Wemustkeepinmindwhatmakessyntheticbiologydifferent

fromallpreviousengineeringdisciplines.Theinsightgained

fromfullyappreciatingthesedifferencesiscriticalfor

developingappropriatestandardsandmethods.