Scytonemin, a yellow-brown pigment found in the sheaths of many cyanobacteria, is believed to be an ancient environmental adaptation to protect against ultraviolet (UV) radiation. Scytonemin’s unique dimeric indolic-phenolic structure, powerful UV-A absorbing properties and biological activity as both an anti-inflammatory and anti-proliferative prompted our study on its biosynthesis. Our investigations focus on the enzymatic mechanisms involved in the formation of the scytonemin monomeric unit including the activation of an aromatic amino acid derived precursor and the unusual ring-forming coupling of the two precursor units. The use of stable isotope incubation studies will allow the identification of the biogenesis of the individual carbons involved in this coupling and heterologous protein expression will enable us to elucidate the functions of the enzymes involved in this mechanism. Increasing levels of UV radiation due to the depletion of the stratospheric ozone layer may have significant environmental impacts including decreasing primary production and increasing the likelihood of human skin traumas such as skin cancer. A better understanding of the enzymatic mechanisms involved in the biosynthesis of naturally occurring UV absorbing natural products such as scytonemin may provide a key opportunity for the development of protective measures against the onslaught of increasing UV radiation.