Barrettides: A Peptide Family Specifically Produced by the Deep-Sea Sponge Geodia barretti

• Main Authors: Karin Steffen (5031989), Quentin Laborde (11341406), Sunithi Gunasekera (1364190), Colton D. Payne (6635933), K. Johan Rosengren (1346457), Ana Riesgo (276019), Ulf Göransson (1364202), Paco Cárdenas (11804556)
• Format: Dataset
• Language: unknown
• Published: 1753
• Subjects: Biochemistry; Genetics; Inorganic Chemistry; Biological Sciences not elsewhere classified; previously known compounds; compound class amenable; biological starting material; geodia barretti </; amphibalanus improvisus </; natural product discovery; north atlantic deep; newly described barrettides; known peptide sequences; 50 </ sub; silico </; discovery route; – iv; similarity searches; several lines; sequencing data; sea demosponge; nmr spectroscopy; native conformation; microbial symbionts; larval settlement; highly similar; geodiidae ); frequently resulting; evidence suggest; elution experiments; disulfide connectivity; biofouling activity; bay barnacle; barrettide c; alternative genomic; 64 μm; North Atlantic
• Online Access: https://doi.org/10.1021/acs.jnatprod.1c00938.s002

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 (IC 50 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.