Photobiocatalytic Strategies for Organic Synthesis

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(9), P. 5459 - 5520

Published: April 28, 2023

Biocatalysis has revolutionized chemical synthesis, providing sustainable methods for preparing various organic molecules. In enzyme-mediated most reactions involve molecules operating from their ground states. Over the past 25 years, there been an increased interest in enzymatic processes that utilize electronically excited states accessed through photoexcitation. These photobiocatalytic a diverse array of reaction mechanisms are complementary to one another. This comprehensive review will describe state-of-the-art strategies photobiocatalysis synthesis until December 2022. Apart reviewing relevant literature, central goal this is delineate mechanistic differences between general employed field. We organize based on relationship photochemical step and transformations. The include studies, substrate scopes, protein optimization strategies. By clearly defining mechanistically-distinct chemistry, we hope illuminate future synthetic opportunities area.

Language: Английский

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Enzymatic Conversion of CO₂: From Natural to Artificial Utilization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(9), P. 5702 - 5754

Published: Jan. 24, 2023

Enzymatic carbon dioxide fixation is one of the most important metabolic reactions as it allows capture inorganic from atmosphere and its conversion into organic biomass. However, due to often unfavorable thermodynamics difficulties associated with utilization CO

Language: Английский

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From Ground-State to Excited-State Activation Modes: Flavin-Dependent “Ene”-Reductases Catalyzed Non-natural Radical Reactions

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(9), P. 1446 - 1457

Published: April 11, 2024

ConspectusEnzymes are desired catalysts for chemical synthesis, because they can be engineered to provide unparalleled levels of efficiency and selectivity. Yet, despite the astonishing array reactions catalyzed by natural enzymes, many reactivity patterns found in small molecule have no counterpart living world. With a detailed understanding mechanisms utilized catalysts, we identify existing enzymes with potential catalyze that currently unknown nature. Over past eight years, our group has demonstrated flavin-dependent "ene"-reductases (EREDs) various radical-mediated selectivity, solving long-standing challenges asymmetric synthesis.This Account presents development EREDs as general radical reactions. While developed multiple generating radicals within protein active sites, this account will focus on examples where flavin mononucleotide hydroquinone (FMNhq) serves an electron transfer initiator. initial mechanistic hypotheses were rooted electron-transfer-based initiation commonly used synthetic organic chemists, ultimately uncovered emergent unique site. We begin covering intramolecular discussing how activates substrate reduction altering redox-potential alkyl halides templating charge complex between flavin-cofactor. Protein engineering been modify fundamental photophysics these reactions, highlighting opportunity tune systems further using directed evolution. This section highlights range coupling partners termination available reactions.The next intermolecular role enzyme-templated ternary complexes among cofactor, halide, partner gating ensure it only occurs when both substrates bound highlight applications activation mode, including olefin hydroalkylation, carbohydroxylation, arene functionalization, nitronate alkylation. also discusses favor steps elusive solution reductive nitroalkanes. aware several recent EREDs-catalyzed photoenzymatic transformations from other groups. discuss results papers context nuances substrates.These biocatalytic often complement state-of-the-art small-molecule-catalyzed making valuable addition chemist's toolbox. Moreover, underlying principles studied potentially operative cofactor-dependent proteins, opening door different types enzyme-catalyzed anticipate serve guide inspire broad interest repurposing access new transformations.

Language: Английский

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MOF‐Hosted Enzymes for Continuous Flow Catalysis in Aqueous and Organic Solvents

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(18)

Published: Feb. 8, 2022

Fully exploiting the potential of enzymes in cell-free biocatalysis requires stabilization catalytically active proteins and their integration into efficient reactor systems. Although recent years initial steps towards immobilization such biomolecules metal-organic frameworks (MOFs) have been taken, these demonstrations limited to batch experiments aqueous conditions. Here we demonstrate a MOF-based continuous flow enzyme system, with high productivity stability, which is also suitable for organic solvents. Under conditions, stability was increased 30-fold, space-time yield exceeded that obtained other strategies by an order magnitude. Importantly, infiltration MOF did not require additional functionalization, thus allowing time- cost-efficient fabrication biocatalysts using label-free enzymes.

Language: Английский

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Making Enzymes Suitable for Organic Chemistry by Rational Protein Design

ChemBioChem, Journal Year: 2022, Volume and Issue: 23(14)

Published: April 7, 2022

This review outlines recent developments in protein engineering of stereo- and regioselective enzymes, which are prime interest organic pharmaceutical chemistry as well biotechnology. The widespread application enzymes was hampered for decades due to limited enantio-, diastereo- regioselectivity, the reason why most chemists were not interested biocatalysis. attitude began change with advent semi-rational directed evolution methods based on focused saturation mutagenesis at sites lining binding pocket. Screening constitutes labor-intensive step (bottleneck), is various research groups continuing develop techniques generation small smart mutant libraries. Rational enzyme design, traditionally an alternative evolution, provides collections mutants require minimal screening. approach first thermostabilization, did enter field stereoselectivity until later. Computational guides such Rosetta algorithms, HotSpot Wizard metric, machine learning (ML) contribute significantly decision making. newest advancements show that CAST/ISM rational design no longer separate tracks, instead, they have started merge. Indeed, researchers utilizing two approaches learned from each other. Today, toolbox includes primarily because possibility controlling by has ensured reliability when facing synthetic challenges. also written hope undergraduate graduate education will include more so than past.

Language: Английский

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Merging the Non‐Natural Catalytic Activity of Lipase and Electrosynthesis: Asymmetric Oxidative Cross‐Coupling of Secondary Amines with Ketones

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(30)

Published: May 27, 2022

Abstract We describe the enantioselective oxidative cross‐coupling of secondary amines with ketones by combining non‐natural catalytic activity lipase electrosynthesis. Various 2,2‐disubstituted 3‐carbonyl indoles a stereogenic quaternary carbon center were synthesized from 2‐substituted in yields up to 78 % good enantio‐ and diastereoselectivities (up 96 : 4 e.r. >20 1 d.r.). This unprecedented protocol demonstrated that hydrolase catalysis is compatible electrosynthesis, reaction can be carried out organic solvents broad substrate scope stereoselectivity. work provides insights into enzymatic

Language: Английский

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Structural features, temperature adaptation and industrial applications of microbial lipases from psychrophilic, mesophilic and thermophilic origins

International Journal of Biological Macromolecules, Journal Year: 2022, Volume and Issue: 225, P. 822 - 839

Published: Nov. 17, 2022

Language: Английский

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Chemoenzymatic Cascades Combining Biocatalysis and Transition Metal Catalysis for Asymmetric Synthesis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(18)

Published: Feb. 6, 2023

Abstract The combination of catalytic methods provides multiple advantages in organic synthesis, allowing access to diverse molecules a straightforward manner. Merging metal and enzyme catalysis is currently receiving great attention due the possibility assemble C−C coupling, olefin metathesis, hydration other reactions with exquisite stereospecificity displayed by enzymes. Thus, this minireview organized based on action species (Pd, Ru, Au, Ir, Fe…) different Special will be paid design sequential processes concurrent cascades, presenting solutions such as use surfactants or compartmentalization strategies for those cases where incompatibilities could hamper overall process.

Language: Английский

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Hierarchical covalent organic framework-foam for multi-enzyme tandem catalysis

Chemical Science, Journal Year: 2023, Volume and Issue: 14(24), P. 6643 - 6653

Published: Jan. 1, 2023

We have developed a covalent organic framework foam with ordered and disordered pores which can immobilize various enzymes towards one-pot tandem glucose synthesis from CMC excellent recyclability be used in biofuel production.

Language: Английский

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Building Enzymes through Design and Evolution

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(19), P. 12436 - 12444

Published: Sept. 7, 2023

Designing efficient enzymes is a formidable challenge at the forefront of modern biocatalysis. Here, we review recent developments in field and illustrate how interplay between computational design advanced protein engineering has given rise to with diverse activities. Natural proteins have been re-engineered computationally embed designed catalytic sites, affording active catalysts that can be optimized through laboratory evolution enhance efficiency selectivity. Computational tools reliably generate stable de novo shapes backbone geometries beyond those found nature, which serve as idealized templates for hosting sites. Genetic code reprogramming methods used introduce additional functional elements into sites expand range chemistries accessible designer enzymes. Finally, emergence powerful based on deep learning promises transformative impact by greatly increasing speed model accuracy. By bringing together latest experimental enzyme design, are optimistic ambition building useful biocatalysts from scratch within reach.

Language: Английский

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