Oxidation chemistry using enzymes is approaching maturity and practical applicability in organic synthesis. Oxidoreductases (enzymes catalysing redox reactions) enable chemists to perform highly selective and efficient transformations ranging from simple alcohol oxidations to stereoselective halogenations of non‐activated C−H bonds. For many of these reactions, no “classical” chemical counterpart is known. Hence oxidoreductases open up shorter synthesis routes based on a more direct access to the target products. The generally very mild reaction conditions may also reduce the environmental impact of biocatalytic reactions compared to classical counterparts. In this Review, we critically summarise the most important recent developments in the field of biocatalytic oxidation chemistry and identify the most pressing bottlenecks as well as promising solutions.

Enoate reductases from the family of old yellow enzymes (OYEs) can catalyze stereoselective trans‐hydrogenation of activated C=C bonds. Their application is limited by the necessity for a continuous supply of redox equivalents such as nicotinamide cofactors [NAD(P)H]. Visible light‐driven activation of OYEs through NAD(P)H‐free, direct transfer of photoexcited electrons from xanthene dyes to the prosthetic flavin moiety is reported. Spectroscopic and electrochemical analyses verified spontaneous association of rose bengal and its derivatives with OYEs. Illumination of a white light‐emitting‐diode triggered photoreduction of OYEs by xanthene dyes, which facilitated the enantioselective reduction of C=C bonds in the absence of NADH. The photoenzymatic conversion of 2‐methylcyclohexenone resulted in enantiopure (ee>99 %) (R)‐2‐methylcyclohexanone with conversion yields as high as 80–90 %. The turnover frequency was significantly affected by the substitution of halogen atoms in xanthene dyes.

Peroxygenases require a controlled supply of H2O2 to operate efficiently. Here, we propose a photocatalytic system for the reductive activation of ambient O2 to produce H2O2 which uses the energy provided by visible light more efficiently based on the combination of wavelength-complementary photosensitizers. This approach was coupled to an enzymatic system to make formate available as a sacrificial electron donor. The scope and current limitations of this approach are reported and discussed.

In green plants, solar-powered electrons are transferred through sophistically arranged photosystems and are subsequently channelled into the Calvin cycle to generate chemical energy. Inspired by the natural photosynthetic scheme, a photoelectrochemical cell (PEC) is constructed configured with protonated graphitic carbon nitride (p-g-C 3 N 4 ) and carbon nanotube hybrid (CNT/p-g-C 3 N 4 ) film cathode, and FeOOH-deposited bismuth vanadate (FeOOH/BiVO 4 ) photoanode for the production of industrially useful chiral alkanes using an old yellow enzyme homologue from Thermus scotoductus (TsOYE). In the biocatalytic PEC platform, photoexcited electrons provided by the FeOOH/BiVO 4 photoanode are transferred to the robust and self-standing CNT/p-g-C 3 N 4 hybrid film that electrocatalytically reduces flavin mononucleotide (FMN) mediator. The p-g-C 3 N 4 promotes a two-electron reduction of FMN coupled with an accelerated electron transfer by the conductive CNT network. The reduced FMN subsequently delivers the electrons to TsOYE for the highly enantioselective conversion of ketoisophorone to (R)-levodione. Under light illumination (>420 nm) and external bias, (R)-levodione is synthesized with the enantiomeric excess value of above 83%, not influenced by the scale of applied bias, simultaneously exhibiting stable and high current efficiency. The results suggest that the biocatalytic PEC made up of economical materials can selectively synthesize high-value organic chemicals using water as an electron donor.

In this study, we combined photo‐organo redox catalysis and biocatalysis to achieve asymmetric C–H bond functionalization of simple alkane starting materials. The photo‐organo catalyst anthraquinone sulfate (SAS) was employed to oxyfunctionalise alkanes to aldehydes and ketones. We coupled this light‐driven reaction with asymmetric enzymatic functionalisations to yield chiral hydroxynitriles, amines, acyloins and α‐chiral ketones with up to 99 % ee. In addition, we demonstrate functional group interconversion to alcohols, esters and carboxylic acids. The transformations can be performed as concurrent tandem reactions. We identified the degradation of substrates and inhibition of the biocatalysts as limiting factors affecting compatibility, due to reactive oxygen species generated in the photocatalytic step. These incompatibilities were addressed by reaction engineering, such as applying a two‐phase system or temporal and spatial separation of the catalysts. Using a selection of eleven starting alkanes, one photo‐organo catalyst and 8 diverse biocatalysts, we synthesized 26 products and report for the model compounds benzoin and mandelonitrile > 97 % ee at gram scale.