Discovery and Rational Mutagenesis of Methionine Sulfoxide Reductase Biocatalysts To Expand the Substrate Scope of the Kinetic Resolution of Chiral Sulfoxides.
Discovery and Rational Mutagenesis of Methionine Sulfoxide Reductase Biocatalysts To Expand the Substrate Scope of the Kinetic Resolution of Chiral Sulfoxides.
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DOI：
10.1021/acscatal.3c00372
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发表时间：
2023-04-07
期刊：
影响因子：
12.9
通讯作者：
Castagnolo, Daniele
中科院分区：
文献类型：
--
作者：
Anselmi, Silvia;Carvalho, Alexandra T. P.;Serrano-Sanchez, Angela;Ortega-Roldan, Jose L.;Caswell, Jill;Omar, Iman;Perez-Ortiz, Gustavo;Barry, Sarah M.;Moody, Thomas S.;Castagnolo, Daniele
蛋氨酸亚砜还原酶A （MsrA）作为非氧化性生物催化剂在外消旋亚砜的对映选择性动力学分解中得到了应用。这项工作描述了选择性和强大的MsrA生物催化剂的鉴定，能够催化各种芳香和脂肪族手性亚砜在8-64 mM浓度下的对端选择性还原，具有高收率和优异的ees（高达99%）。此外，为了扩大MsrA生物催化剂的底物范围，利用硅对接、分子动力学和结构核磁共振（NMR）研究，通过合理的诱变设计了突变酶库。发现突变酶MsrA33可以催化硫原子上带有非甲基取代基的大体积亚砜底物的动力学分辨率高达99%，克服了现有MsrA生物催化剂的显着局限性。
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.
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影响因子：
4.8
作者：
Le, Dung Tien;Lee, Byung Cheon;Gladyshev, Vadim N.
通讯作者：
Gladyshev, Vadim N.
影响因子：
2.8
作者：
Bassanini, Ivan;Ferrandi, Erica Elisa;Monti, Daniela
通讯作者：
Monti, Daniela
影响因子：
15
作者：
Cogan, DA;Liu, GC;Ellman, JA
通讯作者：
Ellman, JA
DOI：
10.1002/cbic.202000430
发表时间：
2021-01-15
期刊：
Chembiochem : a European journal of chemical biology
影响因子：
--
作者：
Anselmi S;Aggarwal N;Moody TS;Castagnolo D
通讯作者：
Castagnolo D
影响因子：
2.9
作者：
Lowther, WT;Brot, N;Matthews, BW
通讯作者：
Matthews, BW