Abstract:[Background] Marine microorganisms are one of the important biological resources in the complex marine ecological environment. The natural products produced by marine microorganisms are extremely abundant, which are the rich source of drug discovery. [Objective] Exploration of the optimal growth conditions of Streptomyces sp. S52-B, a sponge-derived Streptomyces, and excavation of its secondary metabolites in order to isolate new bioactive natural products. [Methods] According to the "One Strain Many Compounds" strategy, we optimized the cultural conditions of sponge-derived Streptomyces sp. S52-B which are suitable for mycelium growth as well as the production of secondary metabolites. Combining mass spectrometry and characteristic UV absorption spectra, one medium is selected for large scale fermentation. After purification by column chromatography and preparative high performance liquid chromatography (HPLC), the structure of the compounds were elucidated by high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance spectroscopy. [Results] The optimal medium of marine Streptomyces sp. S52-B was determined. Based on UV absorption spectroscopy and mass spectrometry analysis, three compounds with pyrrolo[4,3,2-de]quinolone were isolated and identified from a large scale fermentation using medium A. The chlorinated compounds with the pyrrolo[4,3,2-de]quinolone core structure belongs to the natural product of aminoamides, among which ammosalic acid is a new structure compound. [Conclusion] The aminosamide family compounds are known to have excellent anti-cancer activity. Three aminoamide compounds have been isolated and identified from the sponge-derived Streptomyces sp. S52-B, which not only enriches the structural types of such compounds, but also provides opportunity to combining culture conditions and genomic information to mine new structural active natural products from this strain.