The emergence of nitric oxide in the biosynthesis of bacterial natural products

Nitric oxide (NO) has a broad range of biological utilities including as a biosynthon for bacterial natural products (NPs). The biosyntheses of thaxtomin A and rufomycin require an NO-dependent nitration step where a bacterial NO synthase provides the necessary NO and nitration is catalyzed by a cytochrome P450 homolog. Undiscovered NO-dependent biosynthesis pathways are likely to have similar requirements: a pathway dedicated NO source and a metalloenzyme to catalyze the NO-dependent chemistry. This review discusses the current literature on NO-dependent nitration biosynthesis and relevant enzyme mechanisms. The proposal that NO is important for NN bond containing NPs is also explored, particularly for the formations of nitrosamine and nitramine NPs.