The mechanisms of two diterpene cyclases from streptomycetes—one with an unknown product that was identified as the spirocyclic hydrocarbon spiroviolene and one with the known product tsukubadiene—were investigated in detail by isotope labeling experiments. Although the structures of the products were very different, the cyclization mechanisms of both enzymes proceed through the same initial cyclization reactions, before they diverge towards the individual products, which is reflected in the close phylogenetic relationship of the enzymes. A close relationship: The products of two phylogenetically related diterpene cyclases from streptomycetes were identified. The mechanisms of the enzymes were investigated by extensive labeling experiments. Although the structures of the diterpenes are very different, some steps of the cyclization cascade are very similar, thus suggesting that only minor conformational changes of the substrate are responsible for the formation of the unique products.