The co-culture of microbial strains is able to activate silent biosynthetic gene clusters, leading to the production or improved production of natural compounds that do not occur under laboratory conditions. In this study, a new facultatively halophilic/psychrophilic Streptomyces sp. AC117 was initially isolated from the Sea of Oman. Then, three types of consortia were designed, using Streptomyces sp. AC117 with heat-killed bacterial pathogens, living bacterial pathogens, and environmental strains (Streptomyces and Arthrobacter). The effect of the bacterial consortia on antibacterial activity was studied through the agar well diffusion method. The addition of heat-killed bacterial pathogens to the fermentation medium increased antibacterial activity, particularly when Staphylococcus aureus was supplemented. The compound obtained from the AC117+heat-killed S. aureus was analysed by TLC and the HPLC. Elicitation through the heat-killed S. aureus led to a five-fold growth in antibacterial production. As well, the results of 1H-NMR showed that the resulting compounds were anthraquinone derivatives. This product had a MICs of 4.1 and 6.25 μg/mL against Bacillus subtilis and S. aureus, respectively. These findings demonstrated the effectiveness of co-cultivation as a strategy to obtain secondary bioactive metabolites, hidden in the genome of Streptomyces sp. Marine ecosystems also contain a vast library of unique and novel bioproducts. The investigation of three models of bacterial co-cultures, especially heat-killed S. aureus, could thus bring about remarkable improvements in antibacterial activity. These findings indicate the potential drug use of marine microbes and the importance of culture in the activation of silent genes.

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