Cytochrome P450 monooxygenases play a crucial role in the biosynthesis of many natural products and in the human metabolism of numerous pharmaceuticals. This has inspired synthetic organic and medicinal chemists to exploit them as catalysts in regio-and stereoselective CH-activating oxidation of structurally simple and complex organic compounds such as steroids. However, levels of regio-and stereoselectivity as well as activity are not routinely high enough for real applications. Protein engineering using rational design or directed evolution has helped in many respects, but simultaneous engineering of multiple catalytic traits such as activity, regioselectivity, and stereoselectivity, while overcoming tradeoffs and diminishing returns, remains a challenge. Here we show that the exploitation of information derived from mutability landscapes and molecular dynamics simulations for rationally designing iterative saturation mutagenesis constitutes a viable directed evolution strategy. This combined approach is illustrated by the evolution of P450 BM3 mutants which enable nearly perfect regio-and diastereoselective hydroxylation of five different steroids specifically at the C16-position with unusually high activity, while avoiding activity−selectivity trade-offs as well as keeping the screening effort relatively low. The C16 alcohols are of practical interest as components of biologically active glucocorticoids.

More than 7000 ee determinations are possible per day in the analysis of (+)/(−)‐cyclohexylethylamine 1. This result demonstrates the potential of capillary array electrophoresis (CAE) with chirally modified electrolytes for the determination of the enantiomeric purity of organic compounds.

Doped with up to 70 different metal salts, three semiconductor oxides (TiO2, SnO2, and WO3) formed the basis of three libraries of mixed oxides. From a high‐throughput method, over 30 oxides were found to have activities similar to the well‐studied Pt‐doped TiO2 towards the catalyzed decomposition of a model pollutant 4‐chlorophenol in water on irradiation with visible light. Two of the new materials (Ir‐doped WO3 and Ce‐doped SnO2) have been reproduced by conventional synthesis, and their catalytic activity was confirmed.

Mutational changes in cyclohexanone monooxygenases (CHMOs), for example the introduction of serine at position 432, lead to surprisingly versatile enantioselective biocatalysts that perform particularly well in the air‐mediated partial oxidation of prochiral thioethers (see scheme).