New lessons from ancient life: marine invertebrates as a source of new drugs

Abstract

Introduction: Whether as defence against predators and parasites or as a weapon for hunting, time and natural selection provided animals with a myriad of toxins, antibiotics and other specialised chemical warfare [1]. Time and evolution thus generated a broad range of biomolecules able to interfere with almost every biological pathway, rendering redundant the costly, laborious and high-risk process of designing synthetic compounds. Not surprisingly, given the oceans’ immense biodiversity, bioprospecting the seas for new bio-reactive drugs became a corner stone of the EU ‘Biotechnology for Blue Growth’ strategy. Motivated by the first drugs derived from marine animals, such as Prialt [2], and Portugal’s vast coastline, we have been screening marine invertebrates for novel compounds of biotechnological interest, while aiming at developing the tools that enable efficient marine bioprospecting at all levels of biological organisation: from marine ecology to molecular biology.

Materials and methods: Phyllodocid annelids, the muricid gastropod Nucella and their regular prey (e.g. mussels) were collected from rocky beaches at W and SW Portugal. A battery of techniques, including behaviour-directed assays, cytology, histology, plus biochemichal and molecular tools (like oligonucleotide sequencing and PCR to screen for bacteriome-specific rRNAs) have been applied to identify novel substances, locate their production and assess their properties.

Results: We were able to localise special cells and glands of annelids and gastropods (Figure 1) where many novel substances are produced, stored and secreted. This includes potential toxins [3] and their accompanying enzymes. Also, we isolated novel porphyrin-like pigments (which may be important biocidals and antioxidants) and even proteinaceous fluorochromes from our phyllodocid case-study, Eulalia. Among other results, the findings suggest that the microbiome associated to this species may include novel species of symbiotic bacteria.

Figure 1. Histological section of secretory epithelia of Nucella showing serous cells in the foregut wall (arrow) and salivary glands (sg), where toxins are produced.

Discussion and conclusions: Toxins have unique biotechnological value because they interfere with specific biological pathways. Findings support the choice of Eulalia and Nucella from the Portuguese coast as prime targets for bioprospecting. Still, toxins are just a few among many valuable bioproducts so far disclosed. Altogether, the results show that we are just scraping the tip of the iceberg of novel substances with pharmacological potential from marine invertebrates.

Acknowledgements

The Portuguese Foundation for Science and Technology (FCT) funded of project GreenTech (PTDC/MAR-BIO/0113/2014). UCIBIO and LAQV are financed by national funds from FCT, UID/Multi/04378/2013 and UID/QUI/50006/2013, respectively. Both units are co-financed by ERDF under the PT2020 Partnership Agreement POCI-01-0145-FEDER-007728 (UCIBIO) and POCI-01-0145-FEDER – 007265 (LAQV). FCT is also acknowledged for the grants SFRH/BD/109462/2015 to A.P.R., SFRH/BD/120030/2016 to C.M. and IF/00265/2015 to P.M.C.