A computational protocol to predict suitable redox mediators for substitution of NAD(P)H in P450 monooxygenases

P450s catalyze a wide spectrum of stereo- and regioselective reactions like hydroxylations, epoxidations and dehydrogenations. Therefore biotransformations with P450s are of great relevance to organic synthesis. The use of isolated enzymes offers advantages over the use of whole cells. A key issue for catalytic applications of isolated P450s is the demand for a continuous electron supply to the heme-group. Mediator driven bioelectrocatalysis can help to overcome this problem.For mediator driven bioelectrocatalysis the identification of a suitable mediator is crucial for the fast development of an efficient electro enzymatic process. To this end we have developed a computational screening method based on using freely available software. Calculated electron transfer rates were compared with measured product formation rates. The novel in silico procedure allows a faster identification of suitable mediators for electrochemically driven P450 catalyzed reactions and can be used as screening tool. It may also lead to a massive reduction of experimental effort for the development of bioelectrochemical reaction systems in the future.

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► new in silico docking tool to predict suitable mediators for cofactors substitution with P450s.
► comparison of calculated electron transfer rates with measured product formation rates showed a good correlation.
► computational pre-screening leads to a massive reduction of experimental effort.