In this feature article recent progress and future perspectives of cascade catalysis combining bio/bio or bio/chemo catalysts are presented.

C–H functionalization is a chemically challenging but highly desirable transformation. 2-oxoglutarate-dependent oxygenases (2OGXs) are remarkably versatile biocatalysts for the activation of C–H bonds. In nature, they have been shown to accept both small and large molecules carrying out a plethora of reactions, including hydroxylations, demethylations, ring formations, rearrangements, desaturations, and halogenations, making them promising candidates for industrial manufacture. In this review, we describe the current status of 2OGX use in biocatalytic applications concentrating on 2OGX-catalyzed oxyfunctionalization of amino acids and synthesis of antibiotics. Looking forward, continued bioinformatic sourcing will help identify additional, practical useful members of this intriguing enzyme family, while enzyme engineering will pave the way to enhance 2OGX reactivity for non-native substrates.