Natural product screening methods are arguably the most efficient way to identify novel antibiotics. Exploiting obscure, hard to reach environments, implementing the latest high-throughput next generation sequencing techniques, performing in silico analysis and synthesis/recombinant expression of promising candidates may increase the discovery of unique agents.


Deep-sea sponges were collected (∼1000 m depth) in the North Atlantic Ocean and bacteria were recovered. One strain (EU4) was selected for detailed analysis. Strain EU4 produced an inhibitor into liquid media. This compound was purified using liquid chromatography andmatrix-assisted laser desorption/ionization (MALDI) analysis was performed. In parallel, the draft genome was obtained and analysed using BAGEL-3 and anti SMASH-4.0mining tools. Successful synthetic production was obtained for a candidate identified using antiSMASH.


Analysis ofthedraft genome (5.8Mbp) indicates that strain EU4is a novel member of the Bacillaceae. To date, the produced compound showed activity towards Micrococcus luteus only, while the synthetic compound displays a broad spectrum of activity towards Gram positive and negative bacteria. In addition, based on MALDI analysis, the synthetic and the naturally produced compounds possess different molecular weights, being approximately 4 kDa and 1.7 kDa, respectively.


Bacteria recovered from deep-sea sponges couldpotentially be a rich source for novel compounds. In silico analysis of producer genomes has provided a means of identifying cryptic compounds, not produced in culture. Further study of both compounds, which showed diverse activity spectra, may lead to promising new candidates for development into clinically relevant therapeutics.


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