Baeyer-Villiger oxidation of steroids with cyclopentadecanone monooxygenase

The Baeyer-Villiger (BV) reaction is among the most well-known and commonly applied reactions in organic synthesis. The biolog-ical BV reaction is an important type of bioconversion, utilized for numerous interesting synthetic applications because of its high regio and/or stereoselectivity. BVMOs are NADPH-dependent flavoenzymes that use atmospheric oxygen as "green and free" oxidant. Recently, a new BVMO from Pseudomonas sp. strain HI- 70, namely cyclopentadecanone monooxygenase (CPDMO), was cloned, sequenced and overexpressed in E. coli. The amino acid sequence is quite different from those of cyclohexanone MO and steroid MO, with whom it shows an identity of 31 and 33%respectively. Since steroids represent an important class of natu-ral products with a multitude of pharmacological properties, their catabolism is a viable way of producing new bioactive compounds. The exploration of the substrate-activity space of CPDMO was con-ducted with 33 ketosteroids. The study showed that CPDMO in not only able to direct to and accommodate in the active site flexi-ble rings such as cyclopentadecanone, but also more structurally demanding compounds such as steroids. The enzyme was able to catalyze the BV oxidation of 3-keto and 17-ketosteroids with full control of the regiochemistry of the produced lactones.