Directed Evolution of an FeII-Dependent Halogenase for Asymmetric C(sp3)−H Chlorination

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  • Sabine Duewel, Philipps-Universität Marburg
  • ,
  • Luca Schmermund
  • Tabea Faber, Philipps-Universität Marburg
  • ,
  • Klaus Harms, Philipps-Universität Marburg
  • ,
  • Vasundara Srinivasan, Philipps-Universität Marburg
  • ,
  • Eric Meggers, Philipps-Universität Marburg
  • ,
  • Sabine Hoebenreich, Philipps-Universität Marburg
By using structure-guided directed evolution, the substrate scope of the FeII and α-ketoglutarate dependent halogenase Wi-WelO15 from Westiella intricata HT-29-1 was engineered to enable chemo-, regio-, and diastereoselective chlorination of unactivated C(sp3)–H bonds using NaCl as chlorine source. While FeII dependent enzymes are often oxygen sensitive, variants of this halogenase could be screened in lysates under aerobic conditions. The developed biocatalysts offer a route to mild, late-stage chlorination on milligram scale of non-natural hapalindoles containing a ketone instead of an isonitrile functionality, thereby unlocking them for preparative biocatalysis
OriginalsprogEngelsk
TidsskriftACS Catalysis
Vol/bind10
Nummer2
Sider (fra-til)1272-1277
Antal sider6
ISSN2155-5435
DOI
StatusUdgivet - jan. 2020
Eksternt udgivetJa

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