Directed Evolution of an FeII-Dependent Halogenase for Asymmetric C(sp3)–H Chlorination
| Autor: | Sabrina Hoebenreich, Klaus Harms, Vasundara Srinivasan, Sabine Duewel, Luca Schmermund, Eric Meggers, Tabea Melanie Faber |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
chemistry.chemical_classification
Ketone 010405 organic chemistry Halogenation Substrate (chemistry) General Chemistry Protein engineering 010402 general chemistry Directed evolution 01 natural sciences Combinatorial chemistry Catalysis 0104 chemical sciences chemistry Dioxygenase Biocatalysis polycyclic compounds |
| Zdroj: | ACS Catalysis. 10:1272-1277 |
| ISSN: | 2155-5435 |
| DOI: | 10.1021/acscatal.9b04691 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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