Octocorals (Cnidaria, Anthozoa Octocorallia) are magnificent repositories of natural products with fascinating and unusual chemical structures and bioactivities of interest to medicine and biotechnology. However, mechanistic understanding of the contribution of microbial symbionts to the chemical diversity of octocorals is yet to be achieved.

Octocorals lack the physical protection of a massive calcium carbonate skeleton typical for scleractinian corals and instead rely heavily on chemical defense mechanisms to resist predation and avoid overgrowth and fouling.

This review demonstrates that the potential of octocoral-associated microbes to serve as prolific sources of novel natural products of interest in applied biotechnology is indisputable. However, much, if not all, of the chemodiversity known so far for these symbionts derives from bacterial and fungal cultures isolated in the laboratory.

Octocoral-Associated Microbes as Natural-Product Manufacturers

It has long been suspected that natural-product biosynthesis by microbial symbionts could contribute significantly to the chemical diversity commonly reported for sessile marine invertebrates.

In the past 20 years, the status of marine symbiotic bacteria as true producers of several chemical structures underlying manifold bioactivities was solidified. Still, many symbionts captured in culture have not been thoroughly explored in terms of their secondary metabolism and natural-product biosynthesis capacities.

To this end, comprehensive genome mining coupled to laboratory experimentation needs to be applied for the already quite diverse panel of cultivatable octocoral symbionts, with apparently promising discoveries to be made if we are to mine the metabolism of cultivatable fungi and bacteria in depth.

Quite clearly, it is imperative that we enlarge our analytical toolbox to integrate the wealth of recently developed metagenomics and next-generation sequencing technologies to the study of the complex microbiomes of octocorals. Although these approaches have been successfully implemented in biodiversity surveys, metagenomics-assisted investigation of natural product biosynthesis by uncultured octocoral symbionts awaits further development.

Dedicated, cultivation-independent experiments hold promise in illuminating the metabolism of a wide diversity of not cultured or hitherto uncultivatable octocoral symbionts and, will be fundamental to allow the identification of microbial gene clusters involved in the biosynthesis of octocoral-derived metabolites in a comprehensive fashion.

If coupled to heterologous expression systems fine-tuned to promote the biosynthesis of specific compounds (which is the case of existing terpenoid production platforms by surrogate bacterial hosts), metagenomics-guided metabolite biosynthesis by octocoral symbionts (from DNA extraction to recombination and expression) could become an alternative route to sustainably harvest novel natural products from lesser-known and hard-to-culture microorganisms.

Such a multidisciplinary undertaken is key to achieving a sustainable response to the urgent industrial demand for novel drugs and enzyme varieties and can only be fostered through increased investment into next-generation biopharmaceuticals research and development, which considers well-grounded and environmentally reasonable exploitation of natural resources.