Anselmi, Silvia;
Carvalho, Alexandra TP;
Serrano-Sanchez, Angela;
Ortega-Roldan, Jose L;
Caswell, Jill;
Omar, Iman;
Perez-Ortiz, Gustavo;
... Castagnolo, Daniele; + view all
(2023)
Discovery and Rational Mutagenesis of Methionine Sulfoxide Reductase Biocatalysts To Expand the Substrate Scope of the Kinetic Resolution of Chiral Sulfoxides.
ACS Catalysis
, 13
(7)
pp. 4742-4751.
10.1021/acscatal.3c00372.
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Abstract
Methionine sulfoxide reductase A (MsrA) enzymes have recently found applications as nonoxidative biocatalysts in the enantioselective kinetic resolution of racemic sulfoxides. This work describes the identification of selective and robust MsrA biocatalysts able to catalyze the enantioselective reduction of a variety of aromatic and aliphatic chiral sulfoxides at 8–64 mM concentration with high yields and excellent ees (up to 99%). Moreover, with the aim to expand the substrate scope of MsrA biocatalysts, a library of mutant enzymes has been designed via rational mutagenesis utilizing in silico docking, molecular dynamics, and structural nuclear magnetic resonance (NMR) studies. The mutant enzyme MsrA33 was found to catalyze the kinetic resolution of bulky sulfoxide substrates bearing non-methyl substituents on the sulfur atom with ees up to 99%, overcoming a significant limitation of the currently available MsrA biocatalysts.
| Type: | Article |
|---|---|
| Title: | Discovery and Rational Mutagenesis of Methionine Sulfoxide Reductase Biocatalysts To Expand the Substrate Scope of the Kinetic Resolution of Chiral Sulfoxides |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acscatal.3c00372 |
| Publisher version: | https://doi.org/10.1021/acscatal.3c00372 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License. |
| Keywords: | Sulfoxide, methionine reductase, MsrA, biocatalysis, mutagenesis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10168273 |
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