The natural products discovery program in our group utilizes deep-sea sediment-derived microorganisms and employs a bio-active guided isolation procedure and one strain many compounds (OSMAC) approach to screen bio-active natural products for practical applications in the medicinal and agricultural industry. OSMAC strategy is employed to stimulate secondary metabolite production through changing culture conditions. In this paper, we applied cultivation-dependent procedure, changing media type, leading to the discovery of a bio-active compound named inthomycin B (1) from a marine-derived Streptomyces sp. YB104. The compound was characterized based on extensive spectroscopic analyses and comparison to that in the reported literature. The quantification of inthomycin B demonstrated that Streptomyces sp. YB104 produced moderate yield of inthomycin B with a yield around 25 mg/l after 14 days. Thus, Streptomyces sp. YB104 was considered to be a useful potential as a first industrial-producing strain of inthomycins.