The enzymatic oxidation of α-CH bonds in cyclic ethers presents a largely unexplored route for the biocatalytic synthesis of aldehydes and lactones. These products are valuable intermediates in the synthesis of fine chemicals, pharmaceuticals, and materials. Here, we demonstrate that the cytochrome P450 BM3 mutant 9-10A F87I(1) catalyzes the selective oxidation of non-activated cyclic ethers. Preliminary results with menthol-derived ethers and simple hydrocarbon ethers indicate regioselective oxidation, establishing a new enzymatic strategy for ether functionalization. This work broadens the scope of enzymatic CH-activation and underscores the potential of engineered P450s for novel oxidative transformations. References (1) J. C. Lewis, S. Bastian, C. S. Bennett, Y. Fu, Y. Mitsude, M. M. Chen, w. A. Greenberg, C. Wong, F. H. Arnold, Proc Natl Acad Sci U S A 2009, 106, 16550-16555.