Regio- and stereoselective oxidation of unactivated C-H bonds remains a considerable hurdle in synthetic chemistry. Although there has been extensive work done to develop transition metal complexes and biological catalysts for this purpose, there has been limited success. Cytochrome P450 monooxygenases, a family of hemeproteins that catalyze oxidative transformations with a high degree of regio- and stereoselectivity, may represent a source of promising biocatalysts. However, work remains in expanding the substrate scope and reducing the need for expensive heterologous redox partners. In this study, we employed a chimeric macrolide biosynthetic P450 PikCD50N-RhFRED with remarkable substrate promiscuity, increased catalytic activity as compared to the wild-type enzyme, and exhibiting self-sufficiency. Using a �substrate engineering� strategy, we demonstrated the ability of PikCD50N-RhFRED to regioselectively hydroxylate undecorated hydrocarbon rings and functionalized macrolactone rings by replacing the natural desosamine sugar. Furthermore, this simplified linker efficiently facilitated PikCD50N-RhFRED oxidation and was easily cleaved.

Simplified linker for regioselective oxidation of C-H bonds by an engineered P450 monooxygenase

244th National Meeting (2012)

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