Biosynthesis of Triacsins

Nitrogen-nitrogen (N-N) bonds are found in a variety of natural products with diverse biological activities, but only two enzymatic pathways resulting in N-N bond formation have been characterized. The triacsin family contains four known congeners isolated from Streptomyces aureofaciens, and is commonly used today for its potent inhibition of acyl-CoA synthetases. Triacsins are notable for their N-hydroxylated triazene moiety, which is not found in any other known natural products. We have recently identified the biosynthetic gene cluster for triacsins in Streptomyces aureofaciens, and further genome mining effort led to the discovery of an additional triacsin native producer. Our in vivo and in vitro analysis also revealed new biosynthetic insights regarding triacsin biosynthesis in Streptomyces.