Coastal countries have traditionally relied on the existing marine resources (e.g., fishing, food, transport, recreation, and tourism) as well as tried to support new economic endeavors (ocean energy, desalination for water supply, and seabed mining). Modern societies and lifestyle resulted in an increased demand for dietary diversity, better health and well-being, new biomedicines, natural cosmeceuticals, environmental conservation, and sustainable energy sources. These societal needs stimulated the interest of researchers on the diverse and underexplored marine environments as promising and sustainable sources of biomolecules and biomass, and they are addressed by the emerging field of marine (blue) biotechnology. Blue biotechnology provides opportunities for a wide range of initiatives of commercial interest for the pharmaceutical, biomedical, cosmetic, nutraceutical, food, feed, agricultural, and related industries. This article synthesizes the essence, opportunities, responsibilities, and challenges encountered in marine biotechnology and outlines the attainment and valorization of directly derived or bio-inspired products from marine organisms. First, the concept of bioeconomy is introduced. Then, the diversity of marine bioresources including an overview of the most prominent marine organisms and their potential for biotechnological uses are described. This is followed by introducing methodologies for exploration of these resources and the main use case scenarios in energy, food and feed, agronomy, bioremediation and climate change, cosmeceuticals, bio-inspired materials, healthcare, and well-being sectors. The key aspects in the fields of legislation and funding are provided, with the emphasis on the importance of communication and stakeholder engagement at all levels of biotechnology development. Finally, vital overarching concepts, such as the quadruple helix and Responsible Research and Innovation principle are highlighted as important to follow within the marine biotechnology field. The authors of this review are collaborating under the European Commission-funded Cooperation in Science and Technology (COST) Action Ocean4Biotech – European transdisciplinary networking platform for marine biotechnology and focus the study on the European state of affairs.

Natural Products (NP) are essential for the discovery of novel drugs and products for numerous biotechnological applications. The NP discovery process is expensive and time-consuming, having as major hurdles dereplication (early identification of known compounds) and structure elucidation, particularly the determination of the absolute configuration of metabolites with stereogenic centers. This review comprehensively focuses on recent technological and instrumental advances, highlighting the development of methods that alleviate these obstacles, paving the way for accelerating NP discovery towards biotechnological applications. Herein, we emphasize the most innovative high-throughput tools and methods for advancing bioactivity screening, NP chemical analysis, dereplication, metabolite profiling, metabolomics, genome sequencing and/or genomics approaches, databases, bioinformatics, chemoinformatics, and three-dimensional NP structure elucidation.

The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.

During cell activation, mitochondria play an important role in Ca²⁺ homoeostasis due to the presence of a fast and specific Ca²⁺ channel in its inner membrane, the mitochondrial Ca²⁺ uniporter. This channel allows mitochondria to buffer local cytosolic [Ca²⁺] changes and controls the intramitochondrial Ca²⁺ levels, thus modulating a variety of phenomena from respiratory rate to apoptosis. We have described recently that SB202190, an inhibitor of p38 MAPK (mitogen-activated protein kinase), strongly activated the uniporter. We show in the present study that a series of natural plant flavonoids, widely distributed in foods, produced also a strong stimulation of the mitochondrial Ca²⁺ uniporter. This effect was of the same magnitude as that induced by SB202190 (an approx. 20-fold increase in the mitochondrial Ca²⁺ uptake rate), developed without measurable delay and was rapidly reversible. In intact cells, the mitochondrial Ca²⁺ peak induced by histamine was also largely increased by the flavonoids. Stimulation of the uniporter by either flavonoids or SB202190 did not require ATP, suggesting a direct effect on the uniporter or an associated protein which is not mediated by protein phosphorylation. The most active compound, kaempferol, increased the rate of mitochondrial Ca²⁺ uptake by 85±15% (mean±S.E.M., n=4) and the histamine-induced mitochondrial Ca²⁺ peak by 139±19% (mean±S.E.M., n=5) at a concentration of 1 μM. Given that flavonoids can reach this concentration range in plasma after ingestion of flavonoid-rich food, these compounds could be modulating the uniporter under physiological conditions.

Background and purpose: The thiourea derivative KB‐R7943, originally developed as inhibitor of the plasma membrane Na⁺/Ca²⁺exchanger, has been shown to protect against myocardial ischemia‐reperfusion injury. We have studied here its effects on mitochondrial Ca²⁺fluxes.Experimental approach.: [Ca²⁺] in cytosol, mitochondria and endoplasmic reticulum (ER), and mitochondrial membrane potential were monitored using both luminescent (targeted aequorins) and fluorescent (fura‐2, tetramethylrhodamine ethyl ester) probes in HeLa cells.Key results: KB‐R7943 was also a potent inhibitor of the mitochondrial Ca²⁺uniporter (MCU). In permeabilized HeLa cells, KB‐R7943 inhibited mitochondrial Ca²⁺uptake with a Ki of 5.5±1.3 μM (mean±S.D.). In intact cells, 10μM KB‐R7943 reduced by 80% the mitochondrial [Ca²⁺] peak induced by histamine. KB‐R7943 did not modify the mitochondrial membrane potential and had no effect on the mitochondrial Na⁺/Ca²⁺exchanger. KB‐R7943 inhibited histamine‐induced ER‐Ca²⁺release in intact cells, but not in cells loaded with a Ca²⁺‐chelator to damp cytosolic [Ca²⁺] changes. Therefore, inhibition of ER‐Ca²⁺‐release by KB‐R7943 was probably due to the increased feedback Ca²⁺‐inhibition of inositol 1,4,5‐trisphosphate receptors after MCU block. This mechanism also explains why KB‐R7943 reversibly blocked histamine‐induced cytosolic [Ca²⁺] oscillations in the same range of concentrations required to inhibit MCU.Conclusions and Implications: Inhibition of MCU by KB‐R7943 may contribute to its cardioprotective activity by preventing mitochondrial Ca²⁺‐overload during ischemia‐reperfusion. In addition, the effects of KB‐R7943 on Ca²⁺homeostasis provide new evidence for the role of mitochondria modulating Ca²⁺‐release and regenerative Ca²⁺‐oscillations. Search for permeable and selective MCU inhibitors may yield useful pharmacological tools in the future.British Journal of Pharmacology(2007)151, 647–654; doi:10.1038/sj.bjp.0707260