Novel Biocatalysts from Specialized Metabolism

Enzymes are increasingly recognized as valuable (bio)catalysts that complement existing synthetic methods. However, the range of biotransformations used in the laboratory is limited. Here we give an overview on the biosynthesis‐inspired discovery of novel biocatalysts that address various synthetic challenges. Prominent examples from this dynamic field highlight remarkable enzymes for protecting‐group‐free amide formation and modification, control of pericyclic reactions, stereoselective hetero‐ and polycyclizations, atroposelective aryl couplings, site‐selective C−H activations, introduction of ring strain, and N−N bond formation. We also explore unusual functions of cytochrome P450 monooxygenases, radical SAM‐dependent enzymes, flavoproteins, and enzymes recruited from primary metabolism, which offer opportunities for synthetic biology, enzyme engineering, directed evolution, and catalyst design.