
A new article, co-authored by Professor Marcel Jaspars from the University of Aberdeen, was recently published in the Pharmaceutical Journal giving an overview of why marine natural products are a promising prospect for future drug discovery.
Why Marine Natural Products?
Biodiversity in the Earth’s largest habitat, the ocean, is greater than that on land, suggesting a huge potential for new bioactive chemistry. Compounds isolated from marine organisms have novel structures and modulate human disease targets with novel mechanisms of action. Around 15–20 marine-derived compounds have been approved for clinical use against cancer, pain, viral infection and heart disease. Some of the most potent compounds are directed towards cancer cells via linkage to an antibody. The approved marine-derived pharmaceuticals have been produced via (semi)-synthesis, while expression of the biosynthetic gene clusters in a microbial host is a future alternative for the production of those compounds. Technical improvements in the extraction, isolation and structural characterisation of marine-derived compounds, as well as the reduction in effort wasted in isolation of known compounds, have sped up the discovery process, meaning that industry is taking a renewed interest in this field as a source of pharmaceuticals with novel mechanisms of action to treat human disease with unmet need.
Key Points
- Marine invertebrates and microorganisms produce novel marine natural products (MNPs) with potent and selective activity against many human diseases;
- Marine biodiversity is greater than that on land with more than 20 marine animal phyla having no terrestrial representatives;
- The greater the biological diversity investigated, the greater the chemical diversity that will be found — many of these marine-derived pharmaceuticals have novel mechanisms of action;
- About 15–20 compounds of marine origin have been approved for human use against cancer, pain, heart disease and viral infections, with many more in the pipeline;
- Aquaculture, chemical synthesis, and molecular genetics can supply material for clinical trials and clinical use;
- Antibody drug conjugate warheads developed from MNPs continue to feed the early clinical pipeline and offer exciting new avenues for MNP-based therapeutics;
- Although anti-cancer properties have been primarily studied, preclinical pharmacology of novel MNPs has demonstrated antibacterial, antifungal, antimalarial, antituberculosis, antiviral, antidiabetic, anti-inflammatory as well as immune and nervous system bioactivity;
- Understanding the mechanism of action added tremendous value to MNPs as they provide opportunities to decipher new biology that can be exploited to develop first-in-class therapeutics;
- Technical improvements have sped up the time taken to isolate and structurally characterise novel compounds whilst reducing effort wasted on the rediscovery of known compounds;
- These combined scientific advancements mean that pharmaceutical companies now regard marine natural product-derived pharmaceuticals with renewed interest.
Relevance to BlueRemediomics
For the BlueRemediomics project, Professor Marcel Jaspars works on the identification of novel antimicrobial compounds derived from marine microbial communities. This work is part of Work Package 3, which focuses on deriving processes and products from marine microbial communities. This includes the identification of bioactives with cosmeceutical, psychostimulant, antimicrobial or pharmaceutical value as well as the discovery of microbial community processes that can be employed for the upcycling of bioplastics, food waste reduction, and bioremediation of organic pollutants.
The article outlines why marine natural products (MNPs) are an attractive prospect for future drug discovery, provides a history of the field, successes in the clinic and challenges associated with gaining clinical approval, including the need to obtain sufficient amounts of often very complex compounds.