Biosynthesis, enzymology, and future of eunicellane diterpenoids

: Eunicellane diterpenoids are a remarkable family of terpene natural products and have been of high interest for over five decades. Widely distributed in soft corals and rare in plants, eunicellanes were also recently identified in actinobacteria. These terpenoids have foundational 6/10-bicyclic frameworks that are frequently oxidized into structures containing transannular ether bridges. Interest in their unique structures and promising biological activities, such as the paclitaxel-like activities of eleutherobin and the sarcodictyins, has led to advancements in natural product isolation, total synthesis, medicinal chemistry, and drug lead development. Until recently, however, there was little known about the biosynthesis and enzymology of these natural products, but several recent studies in both bacteria and coral have opened up the field. This review summarizes recent advancements in the biosynthesis and enzymology of eunicellane diterpenoids and highlights future research prospects in the field. ONE-SENTENCE SUMMARY: A summary of recent advancements in the biosynthesis and enzymology of eunicellane diterpenoids, a structurally unique and biologically active family of natural products found in coral, plants, and bacteria.