Vornholt, Tobias and Joncev, Zlatko and Sabatino, Valerio and Panke, Sven and Ward, Thomas R. and Sparr, Christof and Jeschek, Markus (2023) An Artificial Metalloenzyme for Atroposelective Metathesis. CHEMCATCHEM, 15 (23). e202301113. ISSN 1867-3880, 1867-3899
Full text not available from this repository. (Request a copy)Abstract
Atropisomers - separable conformers that arise from restricted single-bond rotation - are frequently encountered in medicinal chemistry. However, preparing such compounds with the desired configuration can be challenging. Herein, we present a biocatalytic strategy for achieving atroposelective synthesis relying on artificial metalloenzymes (ArMs). Based on the biotin-streptavidin technology, we constructed ruthenium-bearing ArMs capable of producing atropisomeric binaphthalene compounds through ring-closing metathesis in aqueous media. Further, we show that atroposelectivity can be fine-tuned by engineering two close-lying amino acid residues within the streptavidin host protein. The resulting ArMs promote product formation with enantiomeric ratios of up to 81 : 19, while small-molecule catalysts for atroposelective metathesis under aqueous reaction conditions are yet unknown. This study represents the first demonstration that stereoselective metathesis can be achieved by an artificial metalloenzyme. Atroposelective metathesis catalyzed by artificial enzymes in aqueous solution would provide an attractive and sustainable route to drug molecules and other compounds of interest. We demonstrate that this is possible using artificial metalloenzymes harboring a ruthenium cofactor.**+image
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DIRECTED EVOLUTION; OLEFIN; STREPTAVIDIN; ATROPISOMERISM; CHEMISTRY; Metathesis; Atropisomerism; Biocatalysis; Biotransformations; Artificial Metalloenzymes |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Mikrobiologie (Archaeenzentrum) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2024 07:28 |
| Last Modified: | 20 Mar 2024 07:28 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60222 |
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