Pharmacognosy, Department of Pharmaceutical Biosciences, Biomedical Centre, Uppsala University, Husargatan 3, 751 23 Uppsala, Sweden.
School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
J Nat Prod. 2021 Dec 24;84(12):3138-3146. doi: 10.1021/acs.jnatprod.1c00938. Epub 2021 Dec 7.
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 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 (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 (IC 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.
通过分离和结构阐明来发现天然产物是一项费力的任务，通常需要大量的生物起始材料，并且经常导致先前已知化合物的重新发现。然而，肽是一类可通过对已知肽序列与测序数据进行相似性搜索来进行基因组学、转录组学和发现途径的化合物。基于 barrettides A 和 B 的序列，我们从北大西洋深海海绵 （Geodiidae）中鉴定出了五个新的 barrettide 序列（barrettides C-G）。我们合成、折叠并研究了新描述的 barrettide 之一，barrettide C（NVVPCFCVEDETSGAKTCIPDNCDASRGTNP，二硫键连接 I-IV，II-III）。合成和海绵衍生的 barrettide C 的共洗脱实验证实了其天然构象。NMR 光谱和对幼体附着的抗生物污损活性 （IC 0.64 μM）表明，barrettide C 在结构和功能上均与 barrettides A 和 B 高度相似。有几条证据表明，barrettides 是由海绵本身产生的，而不是其微生物共生体之一产生的。
