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

Опубликована: Авг. 16, 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 metal-loenzymes known to catalyze formation C(sp3)‒CF3 bonds. this work, we demonstrate that nonheme iron enzyme, hydroxy-mandelate 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 metalloenzymes transformations but also creates new enzymatic space organofluorine synthesis.

Язык: Английский

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Protein-Driven Electron-Transfer Process in a Fatty Acid Photodecarboxylase

JACS Au, Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

Naturally occurring photoenzymes are rare in nature, but among them, fatty acid photodecarboxylases derived from Chlorella variabilis (CvFAPs) have emerged as promising photobiocatalysts capable of performing the redox-neutral, light-induced decarboxylation free acids (FAs) into C1-shortened n-alka(e)nes. Using a hybrid QM/MM approach combined with polarizable embedding scheme, we identify structural changes active site and determine energetic landscape forward electron transfer (fET) FA substrate to excited flavin adenine dinucleotide. We obtain charge-transfer diradical structure where water molecule rearranges spontaneously form H-bond interaction flavin, while FA's carboxylate group twists migrates away it. Together, these modifications provide driving force necessary for fET proceed downhill direction. Moreover, by examining R451K mutant is farther core, show that marked reduction electronic coupling counterbalanced an increased force, resulting lifetime similar WT, thereby suggesting resilience process this mutation. Finally, through molecular dynamic simulations, reveal that, following fET, radical occurs within tens picoseconds, overcoming energy barrier ∼0.1 eV. Overall, providing atomistic characterization photoactivation CvFAP, work can be used future protein engineering.

Язык: Английский

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Chiral Sulfones via Single-Electron Oxidation-Initiated Photoenzymatic Catalysis

Synlett, Год журнала: 2024, Номер unknown

Опубликована: Июнь 18, 2024

Abstract We recently achieved an oxidation-initiated photoenzymatic enantioselective hydrosulfonylation of olefins through the utilization a new Gluconobacter ene-reductase mutant (GluER-W100F-W342F). Our method simplifies reaction system by eliminating need for cofactor regeneration mixture and, in contrast with previous systems, does not depend on formation electron donor–acceptor (EDA) complex between substrates and enzyme cofactor. Moreover, GluER variant exhibits good substrate compatibility excellent enantioselectivity. Mechanistic investigations indicate that tyrosine-mediated HAT process is involved support proposed mechanism. In this Synpacts article, we discuss conceptual framework led to discovery reflect key aspects its development. 1 Introduction 2 Conceptual Background 2.1 Intramolecular Photoenzymatic Reactions via Single-Electron Reduction 2.2 Intermolecular 3 The Development Process 4 Conclusion

Язык: Английский

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Creating novel metabolic pathways by protein engineering for bioproduction

Trends in biotechnology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

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