Andrianantoandro-2006-Synthetic biology_ n
- 格式:pdf
- 大小:509.82 KB
- 文档页数:14
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.