Stepping Stones to Synthetic Biology

218 Pages·2018·4.183 MB·English

by  Sergio Carrà

T H E F R O N T I E R S C O L L E C T I O N
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123
THE FRONTIERS COLLECTION
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AvshalomC.Elitzur
IyarTheIsraelInstitutefor,AdvancedResearch,Rehovot,Israel
e-mail:[email protected]
ZeeyaMerali
FoundationalQuestionsInstitute,Decatur,GA30031,USA
e-mail:[email protected]
T.Padmanabhan
InterUniversityCentrefor,AstronomyandAstrophysics(IUCAA),Pune,India
e-mail:[email protected]
MaximilianSchlosshauer
DepartmentofPhysics,UniversityofPortland,Portland,OR97203,USA
e-mail:[email protected]
MarkP.Silverman
DepartmentofPhysics,TrinityCollege,Hartford,CT06106,USA
e-mail:[email protected]
JackA.Tuszynski
DepartmentofPhysics,UniversityofAlberta,Edmonton,ABT6G1Z2,Canada
e-mail:[email protected]
RüdigerVaas
Bild der wissenschaft, Redaktion Astronomie, Physik, 70771 Leinfelden-
Echterdingen,Germany
e-mail:[email protected]
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Sergio Carrà
Stepping Stones to Synthetic
Biology
SergioCarrà
DepartmentofChemistry,
MaterialsandChemicalEngineering
PolytechnicUniversity
Milan,Italy
ISSN1612-3018 ISSN2197-6619 (electronic)
THEFRONTIERSCOLLECTION
ISBN978-3-319-95458-5 ISBN978-3-319-95459-2 (eBook)
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Preface
Thesentence“WhatIcannotcreate,Idonotunderstand”,leftonhisblackboardby
Richard Feynman, echoes the formula “Verum ipsum factum” used by the Italian
philosopherGiambattistaVicotopointtotheguidelineofhisnewscience(Scienza
Nuova,1725)inwhichmancantrulyknowthatwhichisproducedandexecutedby
him.Infact,onlyinthiswaycanheknowtheexactgenesisofthingsintheworld.
ThismessagehasbeenreiteratedbytheAmericanbiotechnologistandbusinessman
Craig Venter, one of the pioneers of the human genome decryption, who asserts:
“What I cannot build, I cannot understand”. With this message, he leads us to the
extraordinaryscientificadventuresofthecreationofanartificialcell.Venterandhis
colleagues have been engaged in investigations into the production of a synthetic
cell, the simplest among the natural ones. Up to now, they have been able to
synthesize specific oligonucleotide molecules that can reproduce themselves after
beinginsertedintoasuitablecelldeprivedofitsnaturalgeneticmaterial.
Theresultrepresentsasignificantstepinaresearchprogrammeaimedatunder-
standing and, in some respects, controlling the life processes. It includes several
research areas that encompass microbiology, physical chemistry and information
theory.Theongoingdevelopmentsappearrelevant,sincetheyofferanengineering
approach to genetics through the perspective of creating life itself, thanks to the
significant results obtained in the control of some networks of chemical reactions
occurringinthecellsandintheprocessesinvolvedincellulartransmissionofmatter
andenergy.
Actually, life should not be thought of only as a chemical event, but also as a
process involving information transmission, because the genome is a repository of
informationgatheredovertimethroughevolution.Applicationoftheaboveconcepts
tomicrobiologicalgrowthisimprovingknowledgeaboutthemechanismsthataffect
theincreaseincomplexityassociatedwithevolutionarypaths.Moreover,itsuggests
analogieswiththeevolutionofthetechnologiesconnectedwiththedevelopmentof
our society. Finally, it suggests approaches for the management of energy trans-
formationsoccurringinlarge-scaleactivities.
v
vi Preface
The aforementioned topics, as well as being characterized by scientific and
philosophical content,areinspiringongoingresearch baptizedassyntheticbiology
and are giving impetus to the employment of bacterial cells as factories for the
conversion of renewable resources to chemical products, whose applications range
from pharmaceuticals to biofuels. In fact, the creation of new reaction pathways
constitutesthecoreofanewfieldcalledmetabolicengineering,whosefocusisthe
activationofbiologicalfunctionsnonexistentinnature.Onthewhole,itrepresentsa
newapproachtoindustrialproductionactivitiescomingoutofthesynergiccombi-
nationofbiology,chemistry,informationtheoryandengineering.
Such topics at the edge of life will be explored, starting from a topical subject
fromthediscussionsinwhichscienceandphilosophymerge,thatis,theconnection
of life processes with the second law of thermodynamics, which, according to Sir
ArthurEddington,“holdsthesupremepositionamongthelawsofNature”.Then,we
move on totheinvestigationinto molecular mechanisms, wherebyorder isformed
outofchaos.
Milan,Italy SergioCarrà
Contents
1 Devils,RatchetsandBiomolecularMotors. . . . . . . . . . . . . . . . . . . 1
1.1 TheCenturyoftheDevils. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 TheUnbearableAttractivenessofIrreversibility. . . . . . . . . . . . . 3
1.3 TheDevilIsaPawl. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.4 SwimminginMolasses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.5 DownintheBioworld. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . 10
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2 EntropyandInformation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.1 BacktoThermodynamics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.2 TheStatisticalCharacterofEntropy. . . . . . . . . . . . . . . . . . . . . . 21
2.3 OutofEquilibrium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.4 ShapingtheWorld. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.5 TheRoleofInformation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2.6 ThePhysicsofNeglecting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
3 AComputerCalledtheUniverse. . . . . . . . . . . . . . . . . . . . . . . . . . . 37
3.1 AControversialOrigin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
3.2 TheAtomicUniverse. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3.3 TheMolecularUniverse. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
3.4 TheBirthofChemistry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
3.5 BacktoEarth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
3.6 TheComputingUniverse. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
4 Biomolecules,NetworksandBioenergetics:SystemApproach
toBiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
4.1 ANewParadigm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
4.2 TheMoleculesofLife. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
4.3 BuildingtheCells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
vii
viii Contents
4.4 Viruses. . . . . . . .. . . . . . . .. . . . . . . .. . . . . . . . .. . . . . . . .. 62
4.5 ThermodynamicsinAction. . . . . . . . . . . . . . . . . . . . . . . . . . . 63
4.6 ThePathofBioenergy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
4.7 LifeandEnergy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
4.8 TamingtheRates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
4.9 TowardsaSystemBiology. . . . . . . . . . . . . . . . . . . . . . . . . . . 76
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
5 MakingSenseofLife. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
5.1 AnEnlighteningContribution. . . . . . . . . . . . . . . . . . . . . . . . . . 83
5.2 TheNatureandRoleofFreeEnergy. . . . . . . . . . . . . . . . . . . . . 84
5.3 TheEighthDayofCreation. . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
5.4 AGentlemen’sClub. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
5.5 CentralDogmaatWork. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
5.6 FeedbackControl. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
5.7 RegulatorGene. . . .. . . . . .. . . . . . .. . . . . .. . . . . .. . . . . .. . 94
5.8 FinalRemark. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
6 ComplexityandInformation:AMetaphorofNatural
andTechnologicalSystems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
6.1 Complexity:APhilosophyoraTool?. . .. . . . . . . .. . . . . . . .. 99
6.2 AWorldPatternedbyNetworks. . . . . . . . . . . . . . . . . . . . . . . 101
6.3 TheLanguageofNature. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
6.4 NaturalComputers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
6.5 AnAbundanceofEnergy(andExergy)fromtheTop. . . . . . . . 108
6.6 TheEmeraldPlanet. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
6.7 EatingtheSun. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
6.8 BacktotheMacroworld. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
6.9 AGlanceTowardstheFuture. . . . . . . . . . . . . . . . . . . . . . . . . 116
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
7 ThePathofEvolution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
7.1 TheInformationalAspectofEvolution. . . . . . . . . . . . . . . . . . . . 121
7.2 EvolutionandComplexity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
7.3 SimulatingEvolution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
7.4 EvolutioninaComputer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
7.5 Meta-BiologicalDarwinism. . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
8 ImitationofLife:TheCellinaSiliconChip. . . . . . . . . . . . . . . . . . 133
8.1 TheChemoton. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
8.2 AChallengingProblem. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
8.3 ModelingofMetabolicReactionSystems. . . . . . . . . . . . . . . . . . 138
8.4 FBAApproach. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
8.5 ExploringtheEscherichiacoli. . . . . . . . . . . . . . . . . . . . . . . . . . 143
Contents ix
8.6 WholeCell. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
9 SyntheticBiologyatWork. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
9.1 TheSyntheticApproachtoBiology. . . . . . . . . . . . . . . . . . . . . . 149
9.2 ProgressinGeneManipulations. . . . . . . . . . . . . . . . . . . . . . . . . 150
9.3 FrontierofGenomeEngineering:TheCRISPR/CasSystem. . . . . 152
9.4 TechnicalIssues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
9.5 WorksinProgress. . . .. . . . . .. . . . . .. . . . . .. . . . . .. . . . . .. 156
9.6 ARenewedSyntheticChemistry. . . . . . . . . . . . . . . . . . . . . . . . 157
9.7 MetabolicEngineering. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
9.8 TowardsaPost-petroleumEra?. . . . . . . . . . . . . . . . . . . . . . . . . 161
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
10 WhyLife?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
10.1 ResurrectingPrometheus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
10.2 TheBeginningofLife. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
10.3 IdeasandTheoriesontheOriginofLife. . . . . . . . . . . . . . . . . . 169
10.3.1 ProteinFirst. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
10.3.2 NucleicAcidsFirst. . . . . . . . . . . . . . . . . . . . . . . . . . . 172
10.3.3 TheChickenortheEgg?. . . . . . . . . . . . . . . . . . . . . . 174
10.3.4 RNAWorld. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176
10.3.5 ThePhaseTransitionApproachtotheEmergence
ofLife. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
10.3.6 BacktoThermodynamics. . . . . . . . . . . . . . . . . . . . . . 180
10.3.7 TheRevengeofEnergy. . . . . . . . . . . . . . . . . . . . . . . 182
10.3.8 AMergingPoint?. . . .. . . . . . .. . . . . . . .. . . . . . . .. 186
10.4 TheFirstSyntheticCell. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Glossary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Sources. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
TitlesinThisSeries. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205