Discovery and Rational Mutagenesis of Methionine Sulfoxide Reductase Biocatalysts to Expand the Substrate Scope of the Kinetic Resolution of Chiral Sulfoxides

Silvia Anselmi, Alexandra T.P. Carvalho, Angela Serrano-Sanchez, Jose L. Ortega-Roldan, Jill Caswell, Iman Omar, Gustavo Perez-Ortiz, Sarah M. Barry, Thomas S. Moody*, Daniele Castagnolo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4742-4751
Number of pages10
JournalACS Catalysis
Volume13
Issue number7
Early online date23 Mar 2023
DOIs
Publication statusPublished - 7 Apr 2023

Keywords

  • biocatalysis
  • methionine reductase
  • MsrA
  • mutagenesis
  • sulfoxide

Fingerprint

Dive into the research topics of 'Discovery and Rational Mutagenesis of Methionine Sulfoxide Reductase Biocatalysts to Expand the Substrate Scope of the Kinetic Resolution of Chiral Sulfoxides'. Together they form a unique fingerprint.

Cite this