Diterpenes are the major defensive small molecules enabling soft corals to survive without a tough exterior skeleton. The potency of coral diterpenes such as the anticancer lead eleutherobin has led to significant biomedical interest. Here, we try to identify and characterize coral-encoded terpene cyclase genes that produce the eunicellane precursor of eleutherobin and cembrene, the precursor of most defensive metabolites found in octocorals.