Biomedical Engineering Reference
In-Depth Information
for.biological.catalysts..Recently,.a.catalyst.reminiscent.of.DNA.polymerase.was.shown.to.
effectively.polymerize.δ-valerolactone.(Takashima.et.al..2011)..The.catalyst.consisted.of.a.
cyclodextrin.heterodimer..One.cyclodextrin.ring.contained.the.catalytic.active.site.and.the.
other.acted.as.a.molecular.clamp.that.secured.the.growing.chain..The.catalyst.was.only.
active.when.the.polymer.chain.was.threaded.through.the.center.of.the.clamp.
These. studies. show. that. the. gap. between. protein. science. and. nanoscale. chemistry. is.
closing.rapidly..As.this.gap.narrows,.we.will.no.longer.be.dependent.on.nature's.examples.
of. nanobiotechnological. artiicial. enzymes,. and. we. will. be. free. to. abandon. protein. and.
nucleic.acids.in.favor.of.whatever.chemical.scaffold.is.best.suited.for.the.task.at.hand.
3.10 Conclusions and Perspectives
Enzymes.are.replacing.traditional.catalysts.and.playing.increasing.roles.in.a.wide.variety.
of.industrial.and.medicinal.applications,.both.in.vivo.(Keasling.2010).and.in.vitro.(Zhang.
et. al.. 2011).. The. ability. to. create. artiicial. enzymes. to. perform. any. desired. chemical.
transformation. would. revolutionize. the. chemical. and. health. industries.. Through. the.
process. of. evolution,. nature. has. found. remarkably. clever. and. eficient. ways. of. solving.
complex. problems.. Biomimicry. has. been. a. valuable. strategy. in. engineering,. product.
design,. and. architecture.. In. nanotechnology. as. well,. close. study. of. natural. examples. of.
functional. nanomachines. will. be. instrumental. to. our. understanding. and. progress.. The.
knowledge.gained.from.the.study.of.natural.and.artiicial.proteins.will.directly.apply.to.
the.development.of.biologically.inspired.nonprotein.nanomachines.
Artiicial. enzyme. design. is. progressing. rapidly,. but. daunting. problems. remain. to. be.
worked. out.. Limitations. in. computational. algorithms. and. processor. power. are. slowly.
relaxing,.but.we.remain.constrained.by.our.poor.understanding.of.the.subtle.mechanisms.
by. which. proteins. do. their. work.. It. is. interesting. that. the. computational. strategy. of.
designing.theozymes.to.stabilize.the.transition.state.has.yielded.enzymes.that.have.similar.
activity.to.catalytic.antibodies,.which.are.raised.to.bind.TSAs..It.may.turn.out.that.“soft”.
bionanomachines.like.proteins.are.too.loppy.to.perform.effective.catalysis.by.transition.
state.stabilization.alone..Proteins.may.have.taken.advantage.of.their.softness.by.evolving.
subtle. catalytic. mechanisms. that. harness. structural. motion. and. transitions. within. the.
protein. to. accelerate. reactions. (Hammes-Schiffer. and. Benkovic. 2006;. Henzler-Wildman.
et. al.. 2007a,b).. Indeed,. the. “lock-and-key”. model. of. enzyme. catalysis. has. fallen. out. of.
style.in.favor.of.the.“induced.it”.model,.in.which.substrate.binding.changes.the.protein.
into. an. active. conformation.. Despite. rapid. improvements. in. computational. power,. such.
subtle. mechanisms. will. remain. extremely. dificult. to. design. for. the. foreseeable. future..
Indeed,.eficient.enzymes.may.prove.to.be.so.complex.and.inely.tuned.as.to.be.chaotic.
and.fundamentally.undesignable.
The. success. of. the. protein. design,. evolution,. and. selection. studies. highlighted. in. this.
review. provides. encouragement. for. the. future.. It. seems. possible. that. while. sequences.
that. encode. highly. eficient. enzymes. are. extremely. rare,. and. to. this. point. have. only.
been.discovered.by.millennia.of.evolution,.sequences.that.encode.poor.catalysts.are.not.
especially.rare..These.sequences.can.be.selected.from.relatively.small.constrained.libraries.
or. designed. computationally.. Poor. catalysts,. while. themselves. not. useful,. can. serve. as.
starting.points.for.optimization.by.directed.evolution,.which.generally.requires.a.starting.
point.with.some.amount.of.the.desired.activity..If.this.activity.has.not.been.found.in.nature,.
