Sponges are prolific
producers of specialized metabolites
with
unique structural scaffolds. Their chemical diversity has always inspired
natural product chemists working in drug discovery. As part of their
metabolic filter-feeding activities, sponges are known to release
molecules, possibly including their specialized metabolites. These
released “Exo-Metabolites” (EMs) may be considered as new chemical reservoirs
that could be collected from the water column while preserving marine
biodiversity. The present work aims to determine the proportion and
diversity of specialized EMs released by the sponge Aplysina cavernicola (Vacelet 1959). This Mediterranean
sponge produces bromo-spiroisoxazoline alkaloids that are widely distributed
in the Aplysinidae family. Aquarium experiments were designed to facilitate
a continuous concentration of dissolved and diluted metabolites from
the seawater around the sponges. Mass Spectrometry (MS)-based metabolomics
combined with a dereplication pipeline were performed to investigate
the proportion and identity of brominated alkaloids released as EMs.
Chemometric analysis revealed that brominated features represented
12% of the total sponge’s EM features. Consequently, a total
of 13 bromotyrosine alkaloids were reproducibly detected as EMs. The
most abundant ones were aerothionin, purealidin L, aerophobin 1, and
a new structural congener, herein named aplysine 1. Their structural
identity was confirmed by NMR analyses following their isolation.
MS-based quantification indicated that these major brominated EMs
represented up to 1.0 ± 0.3% w/w of the concentrated seawater
extract. This analytical workflow and collected results will serve
as a stepping stone to characterize the composition of A. cavernicola’s EMs and those released by
other sponges through in situ experiments, leading
to further evaluate the biological properties of such EMs.
Esculeoside A and tomatine are two major steroidal alkaloids in tomato fruit (Solanum lycopersicum) that exhibit anti-inflammatory, anticancer, and anti-hyperlipidemia activities. Tomatine contained in immature tomato fruit is converted to esculeoside A as the fruit matures. To develop new tomato varieties based on the content analysis of functional secondary metabolites, 184 mutant lines were generated from the original cultivar (S. lycopersicum cv. Micro-Tom) by radiation breeding. Ultra-performance liquid chromatography coupled with evaporative light scattering detector was used to identify the mutant lines with good traits by analyzing tomatine and esculeoside A content. Compared with the original cultivar, candidates for highly functional cultivars with high esculeoside A content were identified in the mature fruit of the mutant lines. The mutant lines with low and high tomatine content at an immature stage were selected as edible cultivars due to toxicity reduction and as a source of tomatine with various pharmacological activities, respectively. During the process of ripening from green to red tomatoes, the rate of conversion of tomatine to esculeoside A was high in the green tomatoes with a low tomatine content, whereas green tomatoes with a high tomatine content exhibited a low conversion rate. Using methanol extracts prepared from unripe and ripe fruits of the original cultivar and its mutant lines and two major compounds, we examined their cytotoxicity against FaDu human hypopharynx squamous carcinoma cells. Only tomatine exhibited cytotoxicity with an IC50 value of 5.589 μM, whereas the other samples did not exhibit cytotoxicity. Therefore, radiation breeding represents a useful tool for developing new cultivars with high quality, and metabolite analysis is applicable for the rapid and objective selection of potential mutant lines.
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