Directed Evolution and Unusual Protonation Mechanism of Pyridoxal Radical C–C Coupling Enzymes for the Enantiodivergent Photobiocatalytic Synthesis of Noncanonical Amino Acids

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Visible light-driven pyridoxal radical biocatalysis has emerged as a new strategy for the stereoselective synthesis of valuable noncanonical amino acids in protecting-group-free fashion. In our previously developed dehydroxylative C–C coupling using engineered PLP-dependent tryptophan synthases, an enzyme-controlled unusual α-stereochemistry reversal and pH-controlled enantiopreference were observed. Herein, through high-throughput photobiocatalysis, we evolved set stereochemically complementary PLP enzymes, allowing both l- d-amino with enhanced enantiocontrol across broad pH window. These newly acid synthases permitted use range organoboron substrates, including boronates, trifluoroborates, boronic acids, excellent efficiency. Mechanistic studies unveiled unexpected racemase activity earlier enzyme variants. This promiscuous was abolished shedding light on origin enantiocontrol. Further mechanistic investigations suggest switch proton donor to account stereoinvertive formation highlighting stereoinversion mechanism that is rare conventional two-electron enzymology.

Язык: Английский

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Ground-state flavin-dependent enzymes catalyzed enantioselective radical trifluoromethylation

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 31, 2025

Язык: Английский

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Enantioselective biosynthesis of vicinal diamines enabled by synergistic photo/biocatalysis consisting of an ene-reductase and a green-light-excited organic dye

CHINESE JOURNAL OF CATALYSIS (CHINESE VERSION), Год журнала: 2025, Номер 68, С. 223 - 229

Опубликована: Янв. 1, 2025

Язык: Английский

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“Excited” Class I Aldolases: EDA Complex Mediated Photo-biocatalytic Enantioselective β-Alkylation of Enals

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 2531 - 2539

Опубликована: Янв. 27, 2025

Язык: Английский

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Mechanistic investigation of repurposed photoenzymes with new-to-nature reactivity

Current Opinion in Green and Sustainable Chemistry, Год журнала: 2025, Номер 52, С. 101009 - 101009

Опубликована: Фев. 27, 2025

Язык: Английский

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SOP-ligand enabled palladium-catalyzed enantioselective anti-Markovnikov hydrothioesterification of α-substituted styrenes

Chinese Chemical Letters, Год журнала: 2025, Номер unknown, С. 111023 - 111023

Опубликована: Март 1, 2025

Язык: Английский

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Synergistic Photoenzymatic Anti-Markovnikov Hydroarylation of Olefins via Heteroaryl Radical Intermediates

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Heteroaromatic alkylations are indispensable reactions for synthesizing biologically active molecules. The anti-Markovnikov hydroarylation of olefins using heteroaryl halides furnishes the product as a single regioisomer; however, catalytic variants ineffective at controlling stereochemical outcome these reactions. Here, we report synergistic photoenzymatic flavin-dependent "ene"-reductases with ruthenium photoredox catalysts. Enzyme homologues were identified, which provide access to both enantiomers in greater than 80% yield up 99:1 er. This method is effective styrenyl- and unactivated alkenes, highlighting generality this approach. highest yielding system involves carboxylated photocatalyst increased affinity enzyme. work expands types radical intermediates that enzymes can use stereoselective intermolecular coupling

Язык: Английский

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Copper‐Catalyzed Cyclopropenation of Alkynes with Difluoromethyl Carbene^†

Chinese Journal of Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Comprehensive Summary The [2+1] cycloaddition of alkynes with fluoroalkyl carbenes represents the most straightforward approach for constructing fluoroalkylated cyclopropenes. However, until now, this strategy has not been applicable to difluoromethyl carbene, as its precursor, diazomethane, tends undergo [3+2] form pyrazoles. This study presents first example copper‐catalyzed cyclopropenation employing difluoroacetaldehyde triftosylhydrazone carbene precursor. A wide range internal and terminal alkynes, featuring diverse functional groups, were efficiently converted into corresponding cyclopropenes in good high yields. Mechanistic investigations, supported by DFT calculations, revealed that bulky Tp Br3 Cu(NCMe) catalyst plays a pivotal role facilitating via concerted pathway.

Язык: Английский

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Biocatalytic Generation of Trifluoromethyl Radicals by Nonheme Iron Enzymes for Enantioselective Alkene Difunctionalization

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Дек. 5, 2024

The trifluoromethyl (-CF

Язык: Английский

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Biocatalytic Generation of Trifluoromethyl Radicals by Nonheme Iron Enzymes for Enantioselective Alkene Difunctionalization

Опубликована: Авг. 19, 2024

The trifluoromethyl (–CF3) group represents a highly prevalent functionality in pharmaceuticals. Over the past few decades, significant advances have been made development of synthetic methods for trifluoromethylation. In contrast, there are currently no metalloenzymes known to catalyze formation C(sp3)‒CF3 bonds. this work, we demonstrate that nonheme iron enzyme, hydroxymandelate synthase from Amycolatopsis orientalis (AoHMS), is capable generating CF3 radicals hypervalent iodine(III) reagents and directing them enantioselective alkene azidation. A high-throughput screening (HTS) platform based on Staudinger ligation was established, enabling rapid evaluation AoHMS variants abiological transformation. final opti-mized variant accepts range substrates, producing azidation products up 73% yield 96:4 enanti-omeric ratio (e.r.). biocatalytic can be further extended pentafluoroethyl diazidation by altering reagent. addition, anion competition experiments provide insights into radical rebound process This study not only expands catalytic repertoire transformations but also creates new enzymatic space organofluorine synthesis.

Язык: Английский

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