C–N and C–S bond formation by cytochrome P450 enzymes

Cytochrome P450 proteins comprise a large family of enzymes that utilize a heme cofactor to perform a diverse array of chemical transformations during secondary metabolite biosynthesis in plants and microorganisms. These enzymes typically catalyze monooxygenation reactions such as hydroxylation and epoxidation, using O₂ as a cosubstrate. However, recent natural product biosynthetic studies revealed that they play crucial roles in morphing the unique architectures of natural products by facilitating atypical carbon–heteroatom bond-forming reactions. In this review, we describe the biosynthetic roles and possible reaction mechanisms of cytochrome P450 enzymes catalyzing unusual carbon–heteroatom bond formation, covering the literature published in the past 5 years.