Marine Drugs

Marine by-products, including fishery discards, seafood-processing residues, aquaculture wastes, crustacean shells, and seaweed-derived side streams, are heterogeneous feedstocks rich in proteins, lipids, minerals, chitinous materials, polysaccharides, and bioactive compounds. This review examines insect-mediated bioconversion as a controlled biorefinery strategy for transforming these unstable marine residues into functional aquafeed ingredients and value-added bioproducts. We compare major marine feedstock classes and industrially relevant insects, with emphasis on substrate–insect matching, moisture control, salinity, lipid and ash load, texture, spoilage risk, and safety. Particular attention is given to how marine substrates can tailor insect meal, insect oil, chitinous fractions, hydrolysates, frass, and functional feed additives. The review further summarizes aquafeed applications of insect-derived products, including fishmeal and fish-oil replacement, protein and amino acid quality, lipid enrichment, gut health, immunity, and disease resistance in aquatic animals. Microbiome-assisted strategies, such as fermentation, enzymatic pretreatment, and gut or substrate microbial management, are discussed as tools to improve substrate stability, digestibility, and product quality. Finally, safety, regulation, scale-up, life cycle assessment, and techno-economic issues are considered. Overall, marine insect biorefineries should be optimized not only for biomass yield, but also for product quality, traceability, and application-specific safety.

The vast majority of the ocean’s microbial natural product biosynthetic potential remains undescribed. To access this chemical diversity, we employed Small Molecule In Situ Resin Capture (SMIRC) across three ecologically distinct sites in San Diego, California. Using high-resolution LC-MS/MS, we detected spatial and temporal variability in the metabolomes captured. Low annotation rates and evidence of extensive halogenation supported the chemical novelty of the compounds captured. We detected rare chlorinated polyketides in the pinnaic acid class, previously known only from filter-feeding invertebrates. We also report the first detection of chlorosulfolipids in the Eastern Pacific Ocean including one that contained 11 chlorine atoms. We linked compound abundances to weekly phytoplankton counts to identify candidate producers and found evidence that different taxa produce chlorosulfolipids of different carbon chain lengths. This study provides evidence of the chemical novelty that can be captured directly from the environment and a framework for integrating environmental metabolomics with phytoplankton counts as a method to identify candidate compound producers.

Tuberculosis therapy is prolonged partly because dormant subpopulations of Mycobacterium tuberculosis show reduced susceptibility to first-line drugs. Therefore, agents active against both replicating and non-replicating mycobacteria remain important to explore. Here, we investigated secondary metabolites from the Indonesian marine-derived fungus Aspergillus ostianus for activity against Mycobacterium smegmatis, a BSL-1 mycobacterial model, under aerobic and hypoxia-induced non-replicating conditions, and examined the underlying mechanism. Bioassay-guided fractionation and spectroscopic analysis identified three hydroxamate pyrazinones: neohydroxyaspergillic acid (NHAA), hydroxyaspergillic acid (HAA), and neoaspergillic acid (NAA). The MIC values were 1.56 µg/mL for NHAA and 3.13 µg/mL for HAA and NAA under both aerobic and hypoxic atmospheres. Time-kill kinetics showed ≥3-log10 CFU reductions within 24–72 h at 4–8× MIC under aerobic conditions and within 48–96 h at 4–8× MIC under hypoxia, with no regrowth at the final sampling point. Scanning electron microscopy and release of UV-absorbing intracellular material at OD₂₆₀/OD₂₈₀ were consistent with envelope disruption in both atmospheres. Antimycobacterial activity was attenuated in a concentration-dependent manner by exogenous Fe³⁺ and was reversed at 100 µM FeCl₃, whereas isoniazid activity was unaffected, supporting iron-reversible and pyrazinone-specific killing. Together with the established Fe³⁺-binding hydroxamate pharmacophore shared by this compound class, these findings support iron sequestration as a plausible mechanism and identify fungal hydroxamate pyrazinones as scaffolds that retain bactericidal activity against hypoxia-adapted non-replicating mycobacteria, warranting further evaluation in M. tuberculosis models.