Terpene Biosynthesis in the Octocorals Erythropodium caribaeorum and Plexaurella spp.

The marine environment is a prolific source of novel compounds for therapeutic
use due to the complex biological and chemical diversity. Throughout the past 30-40
years, over 15,000 natural products have been discovered from the oceans, many of
which display a broad range of potential clinical and commercial applications. Many
marine invertebrates are sessile organisms that lack physical protection, and which
chemical defense may be a possible explanation for these secondary metabolites. Despite
the promise marine natural products have as potent pharmaceutical agents, one of the
major factors delaying clinical use is the supply issue. These bioactive compounds are
often found in trace amounts in the host organism, which makes harvesting from the reefs
unfeasible. A general goal in our lab was to investigate the biosynthesis of secondary
metabolite terpenes to ultimately provide a production method of these potent marine
derived compounds. Eleutherobin and desmethyleleutherobin are diterpenes isolated from the
Caribbean soft coral Erythropodium caribaeorum. These extremely valuable anticancer
agents disrupt cell division by polymerizing and stabilizing microtubules, and have
demonstrated tumor tissue selectivity toward selected breast, renal, ovarian and lung
cancer cell lines. Determining the first intermediate in terpene biosynthesis is the initial
step in developing a biotechnological production method of these cytotoxic agents. We
investigated the complex chemistry of this coral using a radioactivity-guided isolation
procedure, and isolated and partially characterized a diterpene hydrocarbon from E.
caribaeorum.
The close association between marine invertebrates, zooxanthellae and numerous
bacteria gives rise to the question of the identity of the producer of secondary metabolites
in marine organisms. If the symbiont produces these therapeutic agents, cell culture
methods could be employed to supply the compounds rather than obtaining them from
coral reefs. Sesquiterpenes have been isolated from the gorgonian Plexaurella spp.,
however, no investigations concerning host/symbiont contribution of the sesquiterpenes
have been reported. We investigated the biosynthetic source of terpenes in this coral, and
experimental evidence indicates that bacteria are responsible for sesquiterpene
production. We also examined sesquiterpene variation of Plexaurella spp. from various
locations, and found sesquiterpene content to vary within and between species,
identifying Plexaurella as a chemically indistinguishable genus.