Mutagenesis of a Single Site Inverts the Stereopreference of Imine Reductase

ACS Catalysis, Год журнала: 2025, Номер 15(3), С. 2192 - 2199

Опубликована: Янв. 23, 2025

Development of a generally applicable means to invert the stereoselectivity an enzymatic reaction is paramount significance. Through protein structure-guided mutagenesis, Met235 was identified as crucial residue influencing imine reductase AtIRED-catalyzed reduction sterically demanding 1-substituted dihydro-β-carbolines (DHβCs), particularly with single mutants M235A/C/G/I/S/T/V displaying simultaneously inverted and improved catalytic activity relative wild-type (WT) enzyme. Using best variant M235A biocatalyst, five tetrahydro-β-carbolines (THβCs) (R)-configuration were afforded in 48–81% isolated yields 89 → 99% ee. Combined our previous synthesis (S)-stereoisomer using WT other variants, we have established stereocomplementary access these THβCs. Based on solved crystal structure complexed NADP+ substrate 1-t-butyl-DHβC, mutation-induced relief undesired steric clashes rationalized main cause observed inversion enhancement. This influence stereopreference exerted by mutation transferred successfully Y-type IREDs and, part, D-type IREDs, representing first demonstration this kind knowledge transfer between reductases. The current study identifies stereocontrol element it offers potentially generic strategy switch fascinating enzymes.

Язык: Английский

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Continuous-flow chemoenzymatic conversion of racemic alcohols to enantiopure alcohols and amines

Molecular Catalysis, Год журнала: 2025, Номер 580, С. 115094 - 115094

Опубликована: Апрель 8, 2025

Язык: Английский

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Benzothiazolines Acting as Carbanion and Radical Transfer Reagents in Carbon–Carbon Bond Construction

Molecules, Год журнала: 2025, Номер 30(8), С. 1711 - 1711

Опубликована: Апрель 11, 2025

Traditionally employed as hydrogenation reagents, benzothiazolines have emerged versatile carbanion and radical transfer playing a vital role in the construction of various carbon-carbon bonds. The cutting-edge progress photochemistry chemistry prompted study visible light-driven reactions, bringing into vibrant focus. Their chemical processes been uncovered to encompass variety activation mechanisms, with five distinct modes having identified. This work reviews innovative applications donors alkyl or acyl groups, achieving hydroalkylation hydroacylation substitution. By examining their diverse this review highlights potential serving groups for further research development. Moreover, will offer exemplary inspiration synthetic chemists, contributing ongoing evolution utility organic synthesis.

Язык: Английский

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High-Throughput ¹⁹F NMR Chiral Analysis for Screening and Directed Evolution of Imine Reductases

ACS Central Science, Год журнала: 2025, Номер unknown

Опубликована: Июнь 2, 2025

Язык: Английский

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