One major side reaction of the H2-driven styrene epoxidation reaction was the oxidative uncoupling of the FADH2 regeneration from the StyA-catalyzed epoxidation reaction. Due to the high reactivity of reduced flavin species with O2, the desired, StyA-related formation of 4ahydroperoxoflavin yielding the desired epoxidation product competed with the spontaneous aerobic reoxidation of FADH2 yielding H2O2. Although this 'Oxygen Dilemma' severely impedes the StyA-catalyzed epoxidation reaction, it may be a promising approach to promote selective oxyfunctionalization reactions catalyzed by peroxygenases (UPOs). While UPOs rely on H2O2 as stoichiometric oxidant, they are also rapidly inactivated in the presence of excess amounts of H2O2 thereby necessitating precise control over the in situ H2O2 concentration. We therefore coupled the proposed SH-based flavin reduction system to the recombinant peroxygenase from Agrocybe aegerita (rAaeUPO) for selective hydroxylation reactions (Scheme 2, Fig. ). To minimize evaporative loss of the volatile reagents under the non-optimized reaction conditions for the proof-of-concept, we utilized the two liquid phase approach (i.e. applying the substrate as neat organic layer to the aqueous reaction mixture). Under these conditions, 1.5 mM of enantiopure (R)-1-phenylethanol were obtained from ethylbenzene. The overall robustness of the reaction process needed to be improved, as the reaction typically ceased Reaction conditions: 750 µl of KPi buffer pH 7.5 containing 200 µM FMN was added to 750 µl of pure substrate in a two-phase system. The reaction was performed in pressure secured closed vessels with 7 ml excess of headspace filled with gas composed of 40% O2 and 60% H2. The reaction was performed at 30 °C for 4 hours. Sampling was taken from the organic phase. 95 nM of immobilized SH on 210 mg Amberlite TM FPA54 and 4 µM UPO were added to start the reaction. Conversions and ee values were determined by GC-FID analysis. SH = NAD + -reducing hydrogenase, UPO = unspecific peroxygenase. a Total turnover numbers of mol ethylbenzene per mol enzyme or cofactor after 1 h. We attributed this short reaction time to the poor stability of SH in the presence of hydrophobic solvents, which could be alleviated by immobilization of the biocatalyst as demonstrated previously. Hence, we were pleased to observe that using 95 nM of the Amberlite-FPA 54 immobilized SH under identical conditions resulted in the accumulation of 4.4 mM of the enantiomerically pure product. Under these conditions (substituting ethylbenzene with cyclohexane), up to 3.7 mM of cyclohexanol product were obtained (Schema 2, Tab. S4). Notably, the TTN for SH increased from 750 to approx. 46000.