Abstract
Natural product discovery by isolation and structure elucidation is a laborious task often requiring ample quantities of biological starting material and frequently resulting in the rediscovery of previously known compounds. However, peptides are a compound class amenable to an alternative genomic, transcriptomic, and in silico discovery route by similarity searches of known peptide sequences against sequencing data. Based on the sequences of barrettides A and B, we identified five new barrettide sequences (barrettides C–G) predicted from the North Atlantic deep-sea demosponge Geodia barretti (Geodiidae). We synthesized, folded, and investigated one of the newly described barrettides, barrettide C (NVVPCFCVEDETSGAKTCIPDNCDASRGTNP, disulfide connectivity I–IV, II–III). Co-elution experiments of synthetic and sponge-derived barrettide C confirmed its native conformation. NMR spectroscopy and the anti-biofouling activity on larval settlement of the bay barnacle Amphibalanus improvisus (IC50 0.64 μM) show that barrettide C is highly similar to barrettides A and B in both structure and function. Several lines of evidence suggest that barrettides are produced by the sponge itself and not one of its microbial symbionts.
Highlights
Natural product discovery by isolation and structure elucidation is a laborious task often requiring ample quantities of biological starting material and frequently resulting in the rediscovery of previously known compounds
Marine sponges are recognized as a prolific source of new marine natural products (NPs).[1−3] these sponge NPs are frequently found to be produced by their associated microbes.[4−12] Geodia barretti Bowerbank,13 1858 is a species of North Atlantic deep-sea demosponge well studied since the 1980s for its natural products.[14]
An alternative for discovering new peptides is straightforward BLAST searches using known peptide sequences as queries. These searches can be performed on transcriptomes that are abundant in sequencing databases. Such a data survey has the potential to address key challenges in natural product chemistry: (1) Sequencing data can be instrumental in identifying the true producer of NPs.[5,7−11] (2) By discovering new similar sequences, diversity of previously described peptides may be expanded and can be placed in the context of a larger family of compounds
Summary
Natural product discovery by isolation and structure elucidation is a laborious task often requiring ample quantities of biological starting material and frequently resulting in the rediscovery of previously known compounds. We gathered, processed, and refined a collection of sequencing data sets representative of the sponge phylum as a whole and for the species G. barretti in particular (Supporting Information Table S1).
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