Engineering of Methionine Sulfoxide Reductase A with Expanded Substrate Scope for Deracemization of Sulfinyl Esters DOI

Xu Jiang,

Yanli Chen,

Shihuan Zhou

et al.

ACS Sustainable Chemistry & Engineering, Journal Year: 2024, Volume and Issue: 12(32), P. 11987 - 11996

Published: July 29, 2024

Chiral sulfinyl esters are an essential source for preparation of chiral sulfur-containing fine chemicals and pharmaceuticals. However, sustainable enantioselective syntheses optically pure remain to be explored. Herein, we have developed methionine sulfoxide reductase A (MsrA) variants with expanded substrate scope using in silico docking semirational mutagenesis techniques, aimed at preparing enantiopure esters. The variant paMsrA-F59A exhibited exceptional activity enantioselectivity across various esters, yielding the R enantiomers approximately 50% yield 99% enantiomeric excess. Furthermore, this overcame significant limitation wild-type (WT) MsrA, broadening its from methyl ethyl substituents n-propyl/butyl ester substituents. Afterward, by employing conjunction oxidase styrene monooxygenase (SMO), achieved cyclic deracemization racemic obtaining a series (R)-sulfinyl >90% This study successfully providing environmentally friendly strategy efficiently Moreover, our extended application MsrA synthesis compounds bulkier frameworks, highlighting potential green chemistry applications.

Language: Английский

Engineering of Methionine Sulfoxide Reductase A with Expanded Substrate Scope for Deracemization of Sulfinyl Esters DOI

Xu Jiang,

Yanli Chen,

Shihuan Zhou

et al.

ACS Sustainable Chemistry & Engineering, Journal Year: 2024, Volume and Issue: 12(32), P. 11987 - 11996

Published: July 29, 2024

Chiral sulfinyl esters are an essential source for preparation of chiral sulfur-containing fine chemicals and pharmaceuticals. However, sustainable enantioselective syntheses optically pure remain to be explored. Herein, we have developed methionine sulfoxide reductase A (MsrA) variants with expanded substrate scope using in silico docking semirational mutagenesis techniques, aimed at preparing enantiopure esters. The variant paMsrA-F59A exhibited exceptional activity enantioselectivity across various esters, yielding the R enantiomers approximately 50% yield 99% enantiomeric excess. Furthermore, this overcame significant limitation wild-type (WT) MsrA, broadening its from methyl ethyl substituents n-propyl/butyl ester substituents. Afterward, by employing conjunction oxidase styrene monooxygenase (SMO), achieved cyclic deracemization racemic obtaining a series (R)-sulfinyl >90% This study successfully providing environmentally friendly strategy efficiently Moreover, our extended application MsrA synthesis compounds bulkier frameworks, highlighting potential green chemistry applications.

Language: Английский

Citations

2