Marine mollusks comprise a group of shelled and shell-less soft-bodied animals. Heterobranchs, as shell-less, often colorful, and slow-moving animals, rely extensively on chemical defense for their survival, and many of these agents are dietary derivates, resulting from selective feeding and accumulation, and usually after certain transformation. This phenomenon provides researchers with a screening model that is different from traditional methods to find lead compounds of physiologically active drugs from nature.

In recent years, the chemical ecological relationship (prey-predator relationship) between mollusks and their upstream and downstream food chain organisms has become a frontier hotspot in marine natural product research. The marine mollusk-derived secondary metabolites have been found to have important ecological significance and special therapeutical potential, which has led to the elucidation of the chemical ecological relationship between them and their preys or predators. At the same time, small-molecule compounds with chemical defense functions also showed novel chemical diversity and wide range of biological activities and are being studied for drug-related development. Mollusks have become an important class of drug source organisms in the research of new marine drugs.

On August 9, the marine drug research group leading by Prof. GUO Yue-Wei from Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences, published a review paper in Nat. Prod. Rep., summarizing the recent advance on the interesting secondary metabolites from marine mollusks, focusing on their structural features, possible chemo-ecological significance, and promising biological activities.

The research team first summarized the taxonomy of different species of mollusks reported in the past decade and found that they can be traced back to five subclasses (Autobranchia, Caenogastropoda, Heterobranchia, Patellogastropoda and Vetigastropoda). Then, the team aggregated the global distribution of mollusks studied in the last decade according to the collection place. Next, the researchers classified more than 300 secondary metabolites from mollusks according to their structural types, including 33 peptides, 38 alkaloids, 192 terpenes, 54 polyketides, 20 steroids and 20 miscellaneous, and clarified the probable origin (prey-predator relationship with mollusks), structural identification, and reported therapeutical potential. Among them, peptides showed significant cytotoxicity and neuroregulatory activity, and some alkaloids and macrolides showed potent cytotoxicity. These results provide an important reference for finding drug lead compounds from the ocean.

The researchers also discussed on the ecological significance of each type of compounds from the perspective of the different structure types. Among them, most compounds could be recognized as chemical markers of the "predator-prey" chemical ecological relationship between mollusks and their food sources (such as algae, sponges, corals, etc.), and a few compounds could be recognized as markers of symbiotic/parasitic relationship between mollusks and bacteria. Interestingly, many sacoglossans (such as Plakobranchus ocellatus) could sequester the algae chloroplasts to photo-biosynthesize γ-pyrone polypropionates, which was a phenomenon known as "kleptoplasty".

The research of chemical ecology provides important clues for finding molecular types with pharmacological activity from mollusks more quickly, which has offered a new insight into the research of marine natural medicines and provides a new idea for multi-dimensionally revealing the druggability of natural products.

Link:
https://pubs.rsc.org/en/content/articlelanding/2022/NP/D2NP00021K
DOI:
https://doi.org/10.1039/D2NP00021K

CONTACT:
DIAO Wentong
Shanghai Institute of Materia Medica
E-mail: diaowentong@simm.ac.cn