Journal article Open Access

Enzyme engineering: Reaching the maximal catalytic efficiency peak

Moshe Goldsmith; Dan S. Tawfik


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  <identifier identifierType="URL">https://zenodo.org/record/1468296</identifier>
  <creators>
    <creator>
      <creatorName>Moshe Goldsmith</creatorName>
      <affiliation>Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel</affiliation>
    </creator>
    <creator>
      <creatorName>Dan S. Tawfik</creatorName>
      <affiliation>Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Enzyme engineering: Reaching the maximal catalytic efficiency peak</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2017</publicationYear>
  <subjects>
    <subject>optimization plateaus</subject>
    <subject>catalytic efficiency</subject>
  </subjects>
  <dates>
    <date dateType="Issued">2017-12-01</date>
  </dates>
  <language>en</language>
  <resourceType resourceTypeGeneral="JournalArticle"/>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/1468296</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1016/j.sbi.2017.09.002</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="https://creativecommons.org/licenses/by/4.0/legalcode">Creative Commons Attribution 4.0 International</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;The practical need for highly efficient enzymes presents new challenges in enzyme engineering, in particular, the need to improve catalytic turnover (kcat) or efficiency (kcat/KM) by several orders of magnitude. However, optimizing catalysis demands navigation through complex and rugged fitness landscapes, with optimization trajectories often leading to strong diminishing returns and dead-ends. When no further improvements are observed in library screens or selections, it remains unclear whether the maximal catalytic efficiency of the enzyme (the catalytic &amp;#39;fitness peak&amp;#39;) has been reached; or perhaps, an alternative combination of mutations exists that could yield additional improvements. Here, we discuss fundamental aspects of the process of catalytic optimization, and offer practical solutions with respect to overcoming optimization plateaus.&lt;/p&gt;</description>
  </descriptions>
  <fundingReferences>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/501100000780</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/H2020/686330/">686330</awardNumber>
      <awardTitle>Transforming the future of agriculture through synthetic photorespiration</awardTitle>
    </fundingReference>
  </fundingReferences>
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