Light has received increased attention for various chemical reactions but also in combination with biocatalytic reactions. Because currently only a few enzymatic reactions are known, which per se require light, most transformations involving light and a biocatalyst exploit light either for providing the cosubstrate or cofactor in an appropriate redox state for the biotransformation. In selected cases, a promiscuous activity of known enzymes in the presence of light could be induced. In other approaches, light-induced chemical reactions have been combined with a biocatalytic step, or light-induced biocatalytic reactions were combined with chemical reactions in a linear cascade. Finally, enzymes with a light switchable moiety have been investigated to turn off/on or tune the actual reaction. This Review gives an overview of the various approaches for using light in biocatalysis.

Biocatalysis, using enzymes for organic synthesis, has emerged as powerful tool for the synthesis of active pharmaceutical ingredients (APIs). The first industrial biocatalytic processes launched in the first half of the last century exploited whole-cell microorganisms where the specific enzyme at work was not known. In the meantime, novel molecular biology methods, such as efficient gene sequencing and synthesis, triggered breakthroughs in directed evolution for the rapid development of process-stable enzymes with broad substrate scope and good selectivities tailored for specific substrates. To date, enzymes are employed to enable shorter, more efficient, and more sustainable alternative routes toward (established) small molecule APIs, and are additionally used to perform standard reactions in API synthesis more efficiently. Herein, large-scale synthetic routes containing biocatalytic key steps toward >130 APIs of approved drugs and drug candidates are compared with the corresponding chemical protocols (if available) regarding the steps, reaction conditions, and scale. The review is structured according to the functional group formed in the reaction.

European Union's Horizon 2020 program Marie Skłodowska-Curie (764920) for funding. We are grateful to the industrial affiliates of the Centre of Excellence for Biocatalysis (CoEBio3) for a studentship to T.M. Scheme 6. AaeUPO-catalyzed hydroxylation of 15 using Au-TiO 2 .Scheme 7. Aryl iodide and sulfinic acid salt cross-coupling model reaction used for reaction optimization.