Biocatalytic reductive aminations with NAD(P)H-dependent enzymes: enzyme discovery, engineering and synthetic applications

Yuan, Bo; Yang, Dameng; Qu, Ge; Turner, Nicholas J.; Sun, Zhoutong

doi:10.1039/d3cs00391d

Cited by 22 publications

(4 citation statements)

References 188 publications

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“…52 This work further expanded upon by Taday et al starting from ketoynones to produce cyclic β-enaminones in good yields and excellent enantio- and diastereoselectivity. 53…”

Section: Applications In Synthetic Chemistrymentioning

confidence: 99%

Biocatalysis: landmark discoveries and applications in chemical synthesis

O’Connell,

Barry,

Burke

et al. 2024

Chem. Soc. Rev.

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“…52 This work further expanded upon by Taday et al starting from ketoynones to produce cyclic β-enaminones in good yields and excellent enantio- and diastereoselectivity. 53…”

Section: Applications In Synthetic Chemistrymentioning

confidence: 99%

Biocatalysis: landmark discoveries and applications in chemical synthesis

O’Connell,

Barry,

Burke

et al. 2024

Chem. Soc. Rev.

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“… , The direct asymmetric reductive amination of prochiral ketones is a highly ideal transformation in chiral amine synthesis and was ranked second among the most promising transformations to challenge the pharmaceutical industry, as highlighted by the American Chemical Society’s Green Chemistry Institute . The chemocatalysis-based reductive amination of prochiral ketones usually requires expensive transition metal complexes or chiral ligands, which are constrained by side reactions, poor selectivity, and environmental pollution. − Enzyme catalysis presents significant advantages in evolvability, selectivity, and sustainability and is being developed as a complementary approach to traditional chemocatalysis. − The asymmetric synthesis of chiral amines from prochiral ketones can be achieved either through formal reductive amination catalyzed by transaminases − or veritably reductive amination catalyzed by reductive aminases, − imine reductases, − and amine dehydrogenases (AmDHs). − Recently, increasing attention has been paid to the asymmetric synthesis of chiral amines catalyzed by AmDHs because the sole expense is ammonia and the only byproduct is water (Scheme A) …”

Section: Introductionmentioning

confidence: 99%

Shield Machine-like Substrate Walking Strategy-Based Pocket Engineering of F-Amine Dehydrogenase for Accessing Structurally Diverse Fused-Ring and Linked-Ring Aryl Ketones

Wu,

Xu,

Nie

et al. 2024

ACS Catal.

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Although amine dehydrogenases (AmDHs) are emerging as attractive biocatalysts for chiral amine synthesis, their synthetic application in structurally diverse arylamines remains challenging, given the limited substrate acceptance. Substrate walking is an effective coevolution strategy to confer targeted substrate acceptance to an enzyme through a stepwise mutagenesis landscape adaptation. Here, based on the conventional substrate walking strategy, we report a shield machine-like substrate walking strategy to quickly evolve F-BbAmDH from Bacillus badius for accessing the difficult-to-aminate fused-ring and linked-ring aryl ketones. A set of monoring aryl ketone homologues with the benzene ring located at the end of the side-chain and regularly extended carbon skeletons was rationally selected as the transition substrates. A superior mutant library with expanded target fused-ring and linked-ring aryl ketone acceptance was identified based on the activity and specificity enhancement of the transition substrates, enabling the synthesis of pharmaceuticals and bioactive compound-related arylamines with up to 94% yield and 99% ee (R) or 99:1 cis/trans. Structure-based computational results provided molecular insights into the source of the expanded substrate acceptance. Our work demonstrates a concise engineering workflow for the collective acceptance evolution of enzymes for structurally diverse substrate panels and has promising prospects in enzyme engineering.

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“…Herein, we illuminate a nicotinamide-dependent imine reductase (IRED) to enable modular access to chiral amines via a previously elusive remote C(sp 3 )–C(sp 3 ) bond installation strategy (Figure B). In nature, IREDs serve as versatile biocatalysts for catalyzing asymmetric reductive amination of carbonyls with amine donors via a nicotinamide-mediated two-electron hydride transfer mechanism . They boast a broad substrate scope and applicability for industrial production .…”

Section: Introductionmentioning

confidence: 99%

Modular Access to Chiral Amines via Imine Reductase-Based Photoenzymatic Catalysis

Chen,

Li,

Feng

et al. 2024

J. Am. Chem. Soc.

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The development of catalysts serves as the cornerstone of innovation in synthesis, as exemplified by the recent discovery of photoenzymes. However, the repertoire of naturally occurring enzymes repurposed by direct light excitation to catalyze new-to-nature photobiotransformations is currently limited to flavoproteins and ketoreductases. Herein, we shed light on imine reductases (IREDs) that catalyze the remote C(sp 3 )−C(sp 3 ) bond formation, providing a previously elusive radical hydroalkylation of enamides for accessing chiral amines (45 examples with up to 99% enantiomeric excess). Beyond their natural function in catalyzing two-electron reductive amination reactions, upon direct visible-light excitation or in synergy with a synthetic photoredox catalyst, IREDs are repurposed to tune the non-natural photoinduced single-electron radical processes. By conducting wet mechanistic experiments and computational simulations, we unravel how engineered IREDs direct radical intermediates toward the productive and enantioselective pathway. This work represents a promising paradigm for harnessing nature's catalysts for new-to-nature asymmetric transformations that remain challenging through traditional chemocatalytic methods.

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Biocatalytic reductive aminations with NAD(P)H-dependent enzymes: enzyme discovery, engineering and synthetic applications

Abstract: This review summarized NAD(P)H-dependent amine dehydrogenases and imine reductases which catalyzes asymmetric reductive amination to produce optically active amines.

Cited by 22 publications

References 188 publications

Biocatalysis: landmark discoveries and applications in chemical synthesis

Biocatalysis: landmark discoveries and applications in chemical synthesis

Shield Machine-like Substrate Walking Strategy-Based Pocket Engineering of F-Amine Dehydrogenase for Accessing Structurally Diverse Fused-Ring and Linked-Ring Aryl Ketones

Modular Access to Chiral Amines via Imine Reductase-Based Photoenzymatic Catalysis

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