Biocatalysis: landmark discoveries and applications in chemical synthesis

Chemical Society Reviews, Год журнала: 2024, Номер 53(6), С. 2828 - 2850

Опубликована: Янв. 1, 2024

Biocatalysis has become an important tool in chemical synthesis, allowing access to complex molecules with high levels of activity and selectivity low environmental impact. Key discoveries protein engineering, bioinformatics, recombinant technology DNA sequencing have contributed towards the rapid acceleration field. This tutorial review explores enzyme engineering strategies high-throughput screening approaches that been applied for discovery development enzymes synthetic application. Landmark developments field are discussed carefully selected highlight diverse applications within pharmaceutical, agricultural, food industries. The design artificial biocatalytic cascades is also examined. will give readers insight into landmark milestones helped shape grow this branch catalysis since first enzyme.

Язык: Английский

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Learning from Protein Engineering by Deconvolution of Multi‐Mutational Variants

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(36)

Опубликована: Июнь 17, 2024

Abstract This review analyzes a development in biochemistry, enzymology and biotechnology that originally came as surprise. Following the establishment of directed evolution stereoselective enzymes organic chemistry, concept partial or complete deconvolution selective multi‐mutational variants was introduced. Early experiments led to finding mutations can interact cooperatively antagonistically with one another, not just additively. During past decade, this phenomenon shown be general. In some studies, molecular dynamics (MD) quantum mechanics/molecular mechanics (QM/MM) computations were performed order shed light on origin non‐additivity at all stages an evolutionary upward climb. Data used construct unique multi‐dimensional rugged fitness pathway landscapes, which provide mechanistic insights different from traditional landscapes. Along related line, biochemists have long tested result introducing two point enzyme for reasons, followed by comparison respective double mutant so‐called cycles, showed only additive effects, but more recently also uncovered cooperative antagonistic non‐additive effects. We conclude suggestions future work, call unified overall picture epistasis.

Язык: Английский

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Imine Reductases and Reductive Aminases in Organic Synthesis

ACS Catalysis, Год журнала: 2024, Номер unknown, С. 14308 - 14329

Опубликована: Сен. 12, 2024

Язык: Английский

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

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(20), С. 14278 - 14286

Опубликована: Май 10, 2024

The development of catalysts serves as the cornerstone innovation in synthesis, exemplified by recent discovery photoenzymes. However, repertoire naturally occurring enzymes repurposed direct light excitation to catalyze new-to-nature photobiotransformations is currently limited flavoproteins and keto-reductases. Herein, we shed on imine reductases (IREDs) that remote C(sp3)–C(sp3) bond formation, providing a previously elusive radical hydroalkylation enamides for accessing chiral amines (45 examples with up 99% enantiomeric excess). Beyond their natural function catalyzing two-electron reductive amination reactions, upon visible-light or synergy synthetic photoredox catalyst, IREDs are tune non-natural photoinduced single-electron processes. By conducting wet mechanistic experiments computational simulations, unravel how engineered intermediates toward productive enantioselective pathway. This work represents promising paradigm harnessing nature's asymmetric transformations remain challenging through traditional chemocatalytic methods.

Язык: Английский

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Atroposelective Synthesis of Axial Biaryls by Dynamic Kinetic Resolution Using Engineered Imine Reductases

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(41)

Опубликована: Июль 17, 2024

Axially chiral biaryl compounds are ubiquitous scaffolds in natural products, bioactive molecules, ligands and catalysts, but biocatalytic methods for their asymmetric synthesis limited. Herein, we report a highly efficient route the atroposelective of biaryls by dynamic kinetic resolution (DKR). This DKR approach features transient six-membered aza-acetal-bridge-promoted racemization followed an imine reductase (IRED)-catalyzed stereoselective reduction to construct axial chirality under ambient conditions. Directed evolution IRED from Streptomyces sp. GF3546 provided variant (S-IRED-Ss-M11) capable catalyzing process access variety aminoalcohols high yields excellent enantioselectivities (up 98 % yield >99 : 1 enantiomeric ratio). Molecular dynamics simulation studies on S-IRED-Ss-M11 revealed origin its improved activity atroposelectivity. By exploiting substrate promiscuity IREDs power directed evolution, our work further extends biocatalysts' toolbox challenging axially molecules.

Язык: Английский

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A refined picture of the native amine dehydrogenase family revealed by extensive biodiversity screening

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 10, 2024

Язык: Английский

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

ACS Catalysis, Год журнала: 2024, Номер 14(4), С. 2685 - 2695

Опубликована: Фев. 7, 2024

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

Язык: Английский

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Engineering the enantioselectivity of a novel imine reductase from Streptomyces viridochromogenes for the dynamic kinetic reductive amination of cyclic β-ketoester

Molecular Catalysis, Год журнала: 2024, Номер 559, С. 114039 - 114039

Опубликована: Март 23, 2024

Язык: Английский

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Waste Valorization in a Sustainable Bio‐Based Economy: The Road to Carbon Neutrality

Chemistry - A European Journal, Год журнала: 2024, Номер unknown

Опубликована: Сен. 6, 2024

Abstract The development of sustainable chemistry underlying the quest to minimize and/or valorize waste in carbon‐neutral manufacture chemicals is followed over last four five decades. Both chemo‐ and biocatalysis have played an indispensable role this odyssey. particular developments protein engineering, metagenomics bioinformatics preceding three decades a crucial supporting facilitating widespread application both whole cell cell‐free biocatalysis. pressing need, driven by climate change mitigation, for drastic reduction greenhouse gas (GHG) emissions, has precipitated energy transition based on decarbonization defossilization organic production. latter involves biomass CO 2 as feedstock green electricity generated using solar, wind, hydroelectric or nuclear energy. use polysaccharides feedstocks will underpin renaissance carbohydrate with pentoses hexoses base bio‐based solvents polymers environmentally friendly downstream products. availability inexpensive solar led increasing attention electro(bio)catalysis photo(bio)catalysis which turn leading myriad innovations these fields.

Язык: Английский

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Access to Axially Chiral Biaryl Benzylamines via Ancestral Enzyme-Enabled Reductive Amination Desymmetrization

ACS Catalysis, Год журнала: 2025, Номер 15(3), С. 1522 - 1531

Опубликована: Янв. 11, 2025

Axially chiral biaryl benzylamines are present in numerous natural products, pharmaceuticals, ligands, and catalysts. However, the direct catalytic synthesis of these functional molecules using a robust strategy remains formidable challenge. Reductive amination desymmetrization dialdehydes offers powerful approach for construction axially but suffers from extensive undesirable side reactions. Herein, we engineered ancestral imine reductases to enable reductive dialdehydes, allowing wide range with up 99% conversion enantiomeric excess (ee). The ratio product byproducts was 97:3 over 90:10 most cases. This work presents an alternative accessing will stimulate development associated bioactive catalysts/ligands.

Язык: Английский

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