Genome Mining Coupled with OSMAC-Based Cultivation Reveal Differential Production of Surugamide A by the Marine Sponge Isolate Streptomyces sp. SM17 When Compared to Its Terrestrial Relative S. albidoflavus J1074

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.

Metabolomic study of marine Streptomyces sp.: Secondary metabolites and the production of potential anticancer compounds

“…Moreover, a comparison of whole genome regions that contained sur BGCs of each isolate revealed that saline environment-derived sur BGCs likely share more genetic similarities amongst each other, rather than with those from terrestrial environments. The OSMAC approach surprisingly showed that the strain from the marine source produced higher yields of surugamide A in all tested conditions (with and without salt), reaching yields up to >13-fold higher in one of the tested media [ 56 ].…”

Genome Mining as New Challenge in Natural Products Discovery

“…PKU-MA00045 was sequenced and compared to homologues in the published fluostatin gene clusters with BLAST, so identifying the BGCs of these new five compounds. In a similar experiment, Almeida et al [10] used OSMAC approach to identify an octapeptidicsurugamide (Surugamide A) from Streptomyces sp. SM17, isolated from the marine sponge Haliclona simulans.…”

“…Several of these bioactive products are derived from microorganisms, such as fungi and bacteria [6], which have represented an important source of antibiotics and many other medicines [7,8]. In particular many bacteria deriving from the marine environment, particularly those found in association with marine invertebrates (such as sponges), are able to produce secondary metabolites with potential anticancer and antifungal roles because of their cytotoxic properties [9,10]. Considering the great problem of the antimicrobial resistance increase and its high impact on human health, there is an important need of searching for new natural products that could therefore remedy this issue [11,12].…”

Bioactive Molecules from Mangrove Streptomyces qinglanensis 172205

“…The bioinformatics of easily available genome information from microorganisms breaks the bottleneck of traditional natural product discovery to a certain extent, and secondary metabolites isolation guided by genome sequence has increasingly become a research frontier [2]. Genome mining and silent gene cluster activation unveil the potential of diverse secondary metabolites in bacteria [3][4][5]. The OSMAC (One Strain Many Compounds) approach has been proven to be a simple and powerful tool to mine new natural products [6,7].…”