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

preprint
submitted on 30.10.2019 and posted on 05.11.2019 by Sabine Duewel, Luca Schmermund, Tabea Faber, Klaus Harms, Vasundara Srinivasan, Eric Meggers, Sabrina Hoebenreich
By using structure-guided directed evolution, the substrate scope of the FeII and a‑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 new biocatalysts offer a sustainable approach for mild, late-stage chlorination on mg-scale of non-natural hapalindoles containing a ketone instead of an isonitrile functionality, thereby unlocking them for preparative biocatalysis.

History

Email Address of Submitting Author

sabrina.hoebenreich@chemie.uni-marburg.de

Institution

Philipps-Universität Marburg, Fachbereich Chemie

Country

Germany

ORCID For Submitting Author

0000-0002-4715-7123

Declaration of Conflict of Interest

We declare no conflict of interest

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