Traditional and Modern Biomedical Prospecting: Part II—the Benefits: Approaches for a Sustainable Exploitation of Biodiversity (Secondary Metabolites and Biomaterials from Sponges)

The progress in molecular and cell biology has enabled a rational exploitation of the natural resources of the secondary metabolites and biomaterials from sponges (phylum Porifera). It could be established that these natural substances are superior for biomedical application to those obtained by the traditional combinatorial chemical approach. It is now established that the basic structural and functional elements are highly conserved from sponges to the crown taxa within the Protostomia (Drosophila melanogaster and Caenorhabditis elegans) and Deuterostomia (human); therefore, it is obvious that the molecular etiology of diseases within the metazoan animals have a common basis. Hence, the major challenge for scientists studying natural product chemistry is to elucidate the target(s) of a given secondary metabolite, which is per se highly active and selective. After this step, the potential clinical application can be approached. The potential value of some selected secondary metabolites, all obtained from sponges and their associated microorganisms, is highlighted. Examples of compounds that are already in medical use (inhibition of tumor/virus growth [arabinofuranosyl cytosine and arabinofuranosyl adenine]), or are being considered as lead structures (acting as cytostatic and anti-inflammatory secondary metabolites [avarol/avarone], causing induction of apoptosis [sorbicillactone]) or as prototypes for the interference with metabolic pathways common in organisms ranging from sponges to humans (modulation of pathways activated by fungal components [aeroplysinin], inhibition of angiogenesis [2-methylthio-1,4-napthoquinone], immune modulating activity [FK506]) are discussed in this study. In addition, bioactive proteins from sponges are listed (antibacterial activity [pore-forming protein and tachylectin]). Finally, it is outlined that the skeletal elements—the spicules—serve as blueprints for new biomaterials, especially those based on biosilica, which might be applied in biomedicine. These compounds and biomaterials have been isolated/studied by members of the German Center of Excellence BIOTECmarin. The goal for the future is to successfully introduce some of these compounds in the treatment of human diseases in order to raise the public awareness on the richness and diversity of natural products, which should be sustainably exploited for human benefit

Inducible ASABF-Type Antimicrobial Peptide from the Sponge Suberites domuncula: Microbicidal and Hemolytic Activity in Vitro and Toxic Effect on Molluscs in Vivo†

Since sponges, as typical filter-feeders, are exposed to a high load of attacking prokaryotic and eukaryotic organisms, they are armed with a wide arsenal of antimicrobial/cytostatic low-molecular-weight, non-proteinaceous bioactive compounds. Here we present the first sponge agent belonging to the group of ASABF-type antimicrobial peptides. The ASABF gene was identified and cloned from the demosponge Suberites domuncula. The mature peptide, with a length of 64 aa residues has a predicted pI of 9.24, and comprises the characteristic CSα β structural motif. Consequently, the S. domuncula ASABF shares high similarity with the nematode ASABFs; it is distantly related to the defensins. The recombinant peptide was found to display besides microbicidal activity, anti-fungal activity. In addition, the peptide lyses human erythrocytes. The expression of ASABF is upregulated after exposure to the apoptosis-inducing agent 2,2′-dipyridyl. During the process of apoptosis of surface tissue of S. domuncula, grazing gastropods (Bittium sp.) are attracted by quinolinic acid which is synthesized through the kynurenine pathway by the enzyme 3-hydroxyanthranilate 3,4-dioxygenase (HAD). Finally, the gastropods are repelled from the sponge tissue by the ASABF. It is shown that the effector peptide ASABF is sequentially expressed after the induction of the HAD gene and a caspase, as a central enzyme executing apoptosis

Evagination of Cells Controls Bio-Silica Formation and Maturation during Spicule Formation in Sponges

The enzymatic-silicatein mediated formation of the skeletal elements, the spicules of siliceous sponges starts intracellularly and is completed extracellularly. With Suberites domuncula we show that the axial growth of the spicules proceeds in three phases: (I) formation of an axial canal; (II) evagination of a cell process into the axial canal, and (III) assembly of the axial filament composed of silicatein. During these phases the core part of the spicule is synthesized. Silicatein and its substrate silicate are stored in silicasomes, found both inside and outside of the cellular extension within the axial canal, as well as all around the spicule. The membranes of the silicasomes are interspersed by pores of ≈2 nm that are likely associated with aquaporin channels which are implicated in the hardening of the initial bio-silica products formed by silicatein. We can summarize the sequence of events that govern spicule formation as follows: differential genetic readout (of silicatein) → fractal association of the silicateins → evagination of cells by hydro-mechanical forces into the axial canal → and finally processive bio-silica polycondensation around the axial canal. We termed this process, occurring sequentially or in parallel, bio-inorganic self-organization

Aeroplysinin-1, a Sponge-Derived Multi-Targeted Bioactive Marine Drug

Organisms lacking external defense mechanisms have developed chemical defense strategies, particularly through the production of secondary metabolites with antibiotic or repellent effects. Secondary metabolites from marine organisms have proven to be an exceptionally rich source of small molecules with pharmacological activities potentially beneficial to human health. (+)-Aeroplysinin-1 is a secondary metabolite isolated from marine sponges with a wide spectrum of bio-activities. (+)-Aeroplysinin-1 has potent antibiotic effects on Gram-positive bacteria and several dinoflagellate microalgae causing toxic blooms. In preclinical studies, (+)-aeroplysinin-1 has been shown to have promising anti-inflammatory, anti-angiogenic and anti-tumor effects. Due to its versatility, (+)-aeroplysinin-1 might have a pharmaceutical interest for the treatment of different pathologies

Bioactive metabolites from the sponge Suberea sp.

Two new brominated compounds, subereaphenol K (2) and 2-(3,5-dibromo-1-ethoxy-4-oxocyclohexa-2,5-dien-1-yl)acetamide (3), together with subereaphenol B (methyl 2-(2,4-dibromo-3,6-dihydroxyphenyl)acetate; 1) with a revised structure, and five dibromotyrosine-derived metabolites, 4–8, were isolated from the sponge Suberea sp. and characterized by 1D- and 2D-NMR spectroscopic and HR-MS spectrometric data. Compounds 1, 2, 6, and 8 exhibited various weak or moderate bioactivities, including antimicrobial and cytotoxic activities. Furthermore, compounds 1 and 2 inhibited human recombinant phosphodiesterase 4 (PDE4) with IC50 values of 2 μM, whereas compounds 6 and 8 were less active