Show simple item record

dc.contributor.author
Müller, Manuel M.
dc.contributor.author
Allison, Jane R.
dc.contributor.author
Hongdilokkul, Narupat
dc.contributor.author
Gaillon, Laurent
dc.contributor.author
Kast, Peter
dc.contributor.author
van Gunsteren, Wilfred F.
dc.contributor.author
Marlière, Philippe
dc.contributor.author
Hilvert, Donald
dc.date.accessioned
2018-10-30T13:37:49Z
dc.date.available
2017-06-10T14:29:54Z
dc.date.available
2018-10-30T13:37:49Z
dc.date.issued
2013-01-03
dc.identifier.issn
1553-7390
dc.identifier.issn
1553-7404
dc.identifier.other
10.1371/journal.pgen.1003187
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/64273
dc.identifier.doi
10.3929/ethz-b-000064273
dc.description.abstract
The contemporary proteinogenic repertoire contains 20 amino acids with diverse functional groups and side chain geometries. Primordial proteins, in contrast, were presumably constructed from a subset of these building blocks. Subsequent expansion of the proteinogenic alphabet would have enhanced their capabilities, fostering the metabolic prowess and organismal fitness of early living systems. While the addition of amino acids bearing innovative functional groups directly enhances the chemical repertoire of proteomes, the inclusion of chemically redundant monomers is difficult to rationalize. Here, we studied how a simplified chorismate mutase evolves upon expanding its amino acid alphabet from nine to potentially 20 letters. Continuous evolution provided an enhanced enzyme variant that has only two point mutations, both of which extend the alphabet and jointly improve protein stability by >4 kcal/mol and catalytic activity tenfold. The same, seemingly innocuous substitutions (Ile→Thr, Leu→Val) occurred in several independent evolutionary trajectories. The increase in fitness they confer indicates that building blocks with very similar side chain structures are highly beneficial for fine-tuning protein structure and function.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science (PLoS)
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Directed Evolution of a Model Primordial Enzyme Provides Insights into the Development of the Genetic Code
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
PLoS Genetics
ethz.journal.volume
9
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
PLoS Genet
ethz.pages.start
e1003187
en_US
ethz.size
9 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
005410305
ethz.publication.place
San Francisco, CA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02514 - Laboratorium für Organische Chemie / Laboratory of Organic Chemistry::08816 - Kast, Peter (Tit.-Prof.)
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02514 - Laboratorium für Organische Chemie / Laboratory of Organic Chemistry::03492 - Hilvert, Donald (emeritus) / Hilvert, Donald (emeritus)
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02515 - Laboratorium für Physikalische Chemie / Laboratory of Physical Chemistry::03304 - Van Gunsteren, Wilfred F. (emeritus)
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02514 - Laboratorium für Organische Chemie / Laboratory of Organic Chemistry::08816 - Kast, Peter (Tit.-Prof.)
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02514 - Laboratorium für Organische Chemie / Laboratory of Organic Chemistry::03492 - Hilvert, Donald (emeritus) / Hilvert, Donald (emeritus)
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02515 - Laboratorium für Physikalische Chemie / Laboratory of Physical Chemistry::03304 - Van Gunsteren, Wilfred F. (emeritus)
ethz.date.deposited
2017-06-10T14:30:33Z
ethz.source
ECIT
ethz.identifier.importid
imp5936506585fc546271
ethz.ecitpid
pub:102132
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-19T01:38:57Z
ethz.rosetta.lastUpdated
2021-02-15T02:19:54Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Directed%20Evolution%20of%20a%20Model%20Primordial%20Enzyme%20Provides%20Insights%20into%20the%20Development%20of%20the%20Genetic%20Code&rft.jtitle=PLoS%20Genetics&rft.date=2013-01-03&rft.volume=9&rft.issue=1&rft.spage=e1003187&rft.issn=1553-7390&1553-7404&rft.au=M%C3%BCller,%20Manuel%20M.&Allison,%20Jane%20R.&Hongdilokkul,%20Narupat&Gaillon,%20Laurent&Kast,%20Peter&rft.genre=article&rft_id=info:doi/10.1371/journal.pgen.1003187&
 Search print copy at ETH Library

Files in this item

Thumbnail

Publication type

Show simple item record