Photoenzymatic Reductions Enabled by Direct Excitation of Flavin-Dependent “Ene”-Reductases

Sandoval, Braddock A.; Clayman, Phillip D.; Oblinsky, Daniel G.; Oh, Seokjoon; Nakano, Yuji; Bird, Matthew J.; Scholes, Gregory D.; Hyster, Todd K.

doi:10.1021/jacs.0c11494

Cited by 58 publications

(46 citation statements)

References 37 publications

(21 reference statements)

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“…Notably, a significant loss in monooxygenase activity was observed for isolated flavins analogues as compared to flavin in enzyme environment suggesting the crucial role of the noncovalent interactions operating between the apoprotein and flavin cofactor in regulating the functional activity and the substrate specificity in the natural system. 6 While its challenging to investigate the noncovalent interactions within the biological framework, a suitable chemical model is highly desirable to design and develop its biomimetic analogue. Contrary to the natural counterpart, most of the synthetic flavin analogues are designed around charged flavinium core skeleton either as N5-alkylisoalloxaziniums or 5-alkylalloxaziniums or as 1,10-bridged alloxaziniums 7 and reports pertaining to neutral flavin are scarce.…”

Section: Introductionmentioning

confidence: 99%

Modulating catalytic activity of a modified flavin analogue via judicially positioned metal ion toward aerobic sulphoxidation

Mouli

Mishra

2022

RSC Adv.

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Section: Introductionmentioning

confidence: 99%

Modulating catalytic activity of a modified flavin analogue via judicially positioned metal ion toward aerobic sulphoxidation

Mouli

Mishra

2022

RSC Adv.

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“…Overall, our study showcases how non-natural reactivities of native EREDs can be exploited, which also can be further enhanced by protein engineering, if needed, to expand the biocatalyst toolbox and address the long-standing selectivity challenge in radical chemistry. We foresee EREDs and other flavin-dependent enzymes can be further leveraged to generate new synthetically applicable reactivities; this is particularly true as other fields, such as photocatalysis, [20][21][22][35][36][37] are increasingly merging with biocatalysis. 38,39…”

Section: Discussionmentioning

confidence: 99%

Ground-State Electron Transfer as an Initiation Mechanism for Asymmetric Hydroalkylations in Radical Biocatalysis

Fu¹,

Lam²,

Emmanuel³

et al. 2021

Preprint

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Stereoselective bond-forming reactions are essential tools in modern organic synthesis. However, catalytic strategies for controlling the stereochemical outcome of radical-mediated C–C bond formation remain underdeveloped. Here, we report an ‘ene’-reductase catalyzed asymmetric hydroalkylation of olefins using α-bromoketones as radical precursors. In these reactions, radical initiation occurs via ground-state electron transfer from the flavin cofactor located within the enzyme active site, representing a mechanistic departure from previous photoenzymatic hydroalkylations. Four rounds of site saturation mutagenesis based on wild-type nicotinamide-dependent cyclohexanone reductase (NCR) were deployed to access a variant capable of catalyzing a cyclization to furnish β-chiral cyclopentanones with high levels of enantioselectivity. Additionally, the wild-type NCR was identified that could catalyze the intermolecular coupling with precise stereochemical control over the radical termination step. This report demonstrates this enzyme family’s catalytic versatility and highlights the opportunity for protein engineering to address reactivity and selectivity challenges in radical biocatalysis.

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“…The combination of enzymatic catalysis and photochemistry provides numerous perspectives for organic synthesis [110][111][112][113]. This strategy is also an important element of sustainable (green) chemistry.…”

Section: Photochemically Supported Enzymatic Reactionsmentioning

confidence: 99%

Enantioselective synthesis of heterocyclic compounds using photochemical reactions

Hoffmann

2021

Photochem Photobiol Sci

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Different methods for the direct enantioselective photochemical synthesis of heterocycles are presented. Currently, asymmetric catalysis with templates involving hydrogen bonds or metal complexes is intensively investigated. Enzyme catalysis can be simplified under photochemical conditions. For example, in multi enzyme systems, one or more enzyme catalytic steps can be replaced by simple photochemical reactions. Chiral induction in photochemical reactions performed with homochiral crystals is highly efficient. Such reactions can also be carried out with crystalline inclusion complexes. Inclusion of a photochemical substrate and an enantiopure compound in zeolites also leads to enantioselective compounds. In all these methods, the conformational mobility of the photochemical substrates is reduced or controlled. Memory of chirality is a particular case in which a chiral information is temporally lost but the rigid conformations stabilize the molecular structure which leads to the formation of enantiopure compounds. Such studies allows a profound understanding on how particular conformations determine the configuration of the final products.

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Photoenzymatic Reductions Enabled by Direct Excitation of Flavin-Dependent “Ene”-Reductases

Cited by 58 publications

References 37 publications

Modulating catalytic activity of a modified flavin analogue via judicially positioned metal ion toward aerobic sulphoxidation

Modulating catalytic activity of a modified flavin analogue via judicially positioned metal ion toward aerobic sulphoxidation

Ground-State Electron Transfer as an Initiation Mechanism for Asymmetric Hydroalkylations in Radical Biocatalysis

Enantioselective synthesis of heterocyclic compounds using photochemical reactions

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