**Eduardo L. Almeida 1, Navdeep Kaur 2, Laurence K. Jennings 2, Andrés Felipe Carrillo Rincón 1, Stephen A. Jackson 1,3, Olivier P. Thomas <sup>2</sup> and Alan D.W. Dobson 1,3,\***


Received: 12 August 2019; Accepted: 24 September 2019; Published: 26 September 2019

**Abstract:** Much recent interest has arisen in investigating *Streptomyces*isolates derived from the marine environment in the search for new bioactive compounds, particularly those found in association with marine invertebrates, such as sponges. Among these new compounds recently identified from marine *Streptomyces* isolates are the octapeptidic surugamides, which have been shown to possess anticancer and antifungal activities. By employing genome mining followed by an one strain many compounds (OSMAC)-based approach, we have identified the previously unreported capability of a marine sponge-derived isolate, namely *Streptomyces* sp. SM17, to produce surugamide A. Phylogenomics analyses provided novel insights on the distribution and conservation of the surugamides biosynthetic gene cluster (*sur* BGC) and suggested a closer relatedness between marine-derived *sur* BGCs than their terrestrially derived counterparts. Subsequent analysis showed differential production of surugamide A when comparing the closely related marine and terrestrial isolates, namely *Streptomyces* sp. SM17 and *Streptomyces albidoflavus* J1074. SM17 produced higher levels of surugamide A than *S. albidoflavus* J1074 under all conditions tested, and in particular producing >13-fold higher levels when grown in YD and 3-fold higher levels in SYP-NaCl medium. In addition, surugamide A production was repressed in TSB and YD medium, suggesting that carbon catabolite repression (CCR) may influence the production of surugamides in these strains.

**Keywords:** genome mining; OSMAC; phylogenomics; secondary metabolites; surugamides; surugamide A; marine sponge-associated bacteria; *Streptomyces*; *albidoflavus* phylogroup
