Biomedical Engineering Reference
In-Depth Information
3
Artiicial
Enzymes
James A. Stapleton, Agustina Rodriguez-Granillo, and Vikas Nanda
CONTENTS
3.1. Introduction........................................................................................................................... 47
3.2. Directed.Evolution................................................................................................................ 49
3.3. Directed.Evolution.with.Rational.Library.Design........................................................... 52
3.4. Selection.of.Enzymes.with.No.Natural.Parent................................................................ 53
3.5. Catalytic.Antibodies............................................................................................................ 54
3.6. De.Novo.Design.of.Metalloenzymes................................................................................. 55
3.7. De.Novo.Design.of.Enzymes.without.Metal.Cofactors.................................................. 57
3.8. Beyond.Proteins—Artiicial.Ribozymes........................................................................... 59
3.9. Other.Nonprotein.Artiicial.Enzymes............................................................................... 62
3.10. Conclusions.and.Perspectives............................................................................................ 64
References....................................................................................................................................... 65
3.1 Introduction
In.its.purest.deinition,.nanotechnology.describes.the.manipulation.of.matter.at.the.atomic.
level.to.build.systems.from.the.bottom-up.rather.than.the.top-down.(Drexler.1981)..A.materials.
synthesis.strategy.that.pays.attention.to.the.placement.of.each.atom.has.the.potential.to.provide.
huge.gains.in.speciicity,.eficiency,.and.affordability,.and.to.process.enormous.quantities.of.
matter.through.massive.parallelization..The.molecular.machines.from.which.biological.sys-
tems.are.constructed.do.exactly.this..People,.blue.whales,.and.redwood.trees.are.not.carved.
from.larger.blocks.or.injection.molded.but.built.from.the.ground-up,.atom.by.atom.
In. this. chapter,. we. will. discuss. artiicial. enzymes,. a. fascinating. and. promising. area. of.
research. that. has. seen. signiicant. progress. in. recent. years.. Enzymes. are. the. subset. of. bio-
logical.macromolecules.that.catalyze.chemical.reactions..Biological.machines,.which.in.addi-
tion.to.catalysis.perform.structural,.regulatory,.and.other.central.roles.in.biology,.are.natural.
examples. of. “soft”. nanotechnology. from. which. we. can. learn. much. about. design. on. the.
nanoscale..These.machines.self-assemble.and.function.in.water.at.environmental.tempera-
ture.and.pressure..Proteins,.the.dominant.class.of.catalytic.biological.molecules,.are.linear.
polymers.of.amino.acids.that.fold.(in.a.type.of.intramolecular.self.assembly).into.precise.but.
lexible. three-dimensional. structures. determined. by. their. amino. acid. sequence. (Aninsen.
et.al..1961)..Water.is.the.solvent.for.all.life,.and.protein.folding.and.function.take.extensive.
advantage.of.the.range.of.hydrophobic/hydrophilic.properties.of.the.20.natural.amino.acids..
However,.some.proteins.are.stable.and.functional.in.organic.environments.(Klibanov.2001),.
indicating.that.water-insoluble.or.water-incompatible.chemistry.is.not.beyond.their.reach.
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