Unraveling Binding Effects of Cobalt(II) Sepulchrate with the Monooxygenase P450 BM-3 Heme Domain Using Molecular Dynamics Simulations

Verma, Rajni; Schwaneberg, Ulrich; Holtmann, Dirk; Roccatano, Danilo

doi:10.1021/acs.jctc.5b00290

Cited by 6 publications

(3 citation statements)

References 69 publications

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“…70 Also increasing the electron transfer rate between the mediator molecule and the P450 heme-site represents a very promising approach to address the Oxygen Dilemma. [84][85][86][87][88][89][90][91][92] Mechanistically, photochemical reduction is very similar to electrochemical regeneration of P450 monooxygenases. Hence it is not very astonishing that also (in)direct photochemical regeneration of P450 monooxygenases has been investigated.…”

Section: Reductive Regeneration Of Heme-enzymesmentioning

confidence: 99%

Nonconventional regeneration of redox enzymes – a practical approach for organic synthesis?

Zhang

Hollmann

2018

Chem. Commun.

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Oxidoreductases have become useful tools in the hands of chemists to perform selective and mild oxidation and reduction reactions. Instead of mimicking native catalytic cycles, generally involving costly and unstable nicotinamide cofactors, more direct, NAD(P)-independent methodologies are being developed. The promise of these approaches not only lies with simpler and cheaper reaction schemes but also with higher selectivity as compared to whole cell approaches and their mimics.

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Section: Reductive Regeneration Of Heme-enzymesmentioning

confidence: 99%

Nonconventional regeneration of redox enzymes – a practical approach for organic synthesis?

Zhang

Hollmann

2018

Chem. Commun.

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“…The previously mentioned direct cathodic reduction of O 2 can in principle be alleviated by choice of a suitable reactor design minimising the O 2 concentration in the cathode compartment . Similarly, engineering the monooxygenase mediator interaction on the basis of rational design might improve the efficiency of electron transfer . Another possible handle could be the choice of electrode material.…”

Section: Ways To Deal With the Oxygen Dilemmamentioning

confidence: 99%

The Oxygen Dilemma: A Severe Challenge for the Application of Monooxygenases?

2016

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Monooxygenases are promising catalysts because they in principle enable the organic chemist to perform highly selective oxyfunctionalisation reactions that are otherwise difficult to achieve. For this, monooxygenases require reducing equivalents, to allow reductive activation of molecular oxygen at the enzymes' active sites. However, these reducing equivalents are often delivered to O2 either directly or via a reduced intermediate (uncoupling), yielding hazardous reactive oxygen species and wasting valuable reducing equivalents. The oxygen dilemma arises from monooxygenases' dependency on O2 and the undesired uncoupling reaction. With this contribution we hope to generate a general awareness of the oxygen dilemma and to discuss its nature and some promising solutions.

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“…Extensive mutational studies of cytochrome P450 BM3 were already conducted to allow oxidation of a broad range of fine chemical precursors, pharmaceuticals and aromatic compounds, demonstrating the possible areas of application. To overcome the limiting cofactor NADPH, several approaches have addressed alternatives including enzymatic and non‐enzymatic regeneration of NADPH, or avoiding the need for NADPH by using photochemical and electrochemical methods. Energy supply by direct electron transfer (DET), which is regarded as a very progressive method because of its reduced necessary components, has been achieved for several enzymes .…”

Section: Introductionmentioning

confidence: 99%

Surface‐Binding Peptide Facilitates Electricity‐Driven NADPH‐Free Cytochrome P450 Catalysis

et al. 2018

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Industrial biotechnology aims to exploit cytochrome P450 enzymes to access their sophisticated catalytic activity for challenging chemical reactions on inert C−H bonds. Limited by the need for NADPH, approaches to bind P450 enzymes to electrode surfaces for an artificial electron supply are promising. Here, we demonstrate that a recombinant fusion of an indium tin oxide binding peptide and the multi‐domain class VIII cytochrome P450 BM3 can be used in electrically driven catalysis. Bioelectrocatalytic activity is analyzed by direct product quantification resulting in superior activity of the specifically immobilized P450 BM3 in contrast to unspecifically adsorbed enzyme. Spacer and anchor point studies imply that enzyme flexibility and alignment are crucial factors to achieve high activity on the electrode. Furthermore, we demonstrate that our approach is also feasible for pharmaceutical application using naringenin as substrate.

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Unraveling Binding Effects of Cobalt(II) Sepulchrate with the Monooxygenase P450 BM-3 Heme Domain Using Molecular Dynamics Simulations

Cited by 6 publications

References 69 publications

Nonconventional regeneration of redox enzymes – a practical approach for organic synthesis?

Nonconventional regeneration of redox enzymes – a practical approach for organic synthesis?

The Oxygen Dilemma: A Severe Challenge for the Application of Monooxygenases?

Surface‐Binding Peptide Facilitates Electricity‐Driven NADPH‐Free Cytochrome P450 Catalysis

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