Cytochrome P450 monooxygenases (P450s) are ubiquitous hemeproteins that insert oxygen specifically into substrates leading to diverse chemical transformations. Utilizing their capabilities, microbial whole-cell biocatalysts are applied in pharmaceutical and fine chemical industry to produce biomolecules and drug metabolites. In order to synthesize novel bioactive compounds there is a great demand to identify P450s with new reaction and substrate scope. In this study, genome mining and an activity screening were successfully combined to discover so far underutilized biocatalysts. The screening revealed the expected broad range of reactions, such as hydroxylations, dealkylations, reductions and desaturations. For Actinosynnema mirum and ritonavir the biotransformation was transferred to a preparative scale resulting in a ritonavir conversion of 90 % after 48 h and 13 different metabolites analyzed by LC-MS 2 and NMR. These results clearly demonstrate the potential of the underlying approach to identify promising whole cell biocatalysts with good conversion and product scopes.[a] L. . Bacterial and fungal strains selected for activity screening. Shown are total numbers of found P450 sequences for CYPED (black) and PROSITE (green) and the number of homologous families (brown) and superfamilies (red). A: bacterial strains 1 Bradyrhizobium elkanii, 2 Cystobacter fuscus DSM 2262, 3
The Front Cover shows a C−H‐activation reaction carried out by the heme group (orange) of a protein (PDB: 1000). In their Full Paper, Stephan Lütz and co‐workers present the successful identification of novel and versatile P450 biocatalysts by genome mining and its successful scale‐up to a biotransformation reaction on L‐scale. The results show that a large number of catalysts for C−H‐activation is still undiscovered and holds the promise to find more useful catalysts for green oxidation processes. More information can be found in the Full Paper by Lisa Marie Schmitz et al. on page 5766 in Issue 23, 2019 (DOI: 10.1002/cctc.201901273).
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