Marine natural products offer a promising source in the development of new antibiotic drugs. Two previously undescribed compounds, including one sulfur-bearing alkaloid named quinosumycin (1) along with one chromone derivative namely chromycone (2), were discovered from an ethyl acetate (EtOAc) extract of marine Streptomyces diastaticus NBU2966 through a bioactivity-guided isolation prioritized for antimicrobial potential. The analysis of nuclear magnetic resonance spectroscopy (NMR), high resolution electrospray ionization mass spectroscopy (HRESIMS) data, and electronic circular dichroism (ECD) calculations enabled the elucidation of their structures and the determination of their absolute configurations. Quinosumycin (1) is the first heterodimer scaffold incorporating quinolinone and quinazolinone motifs coupled by a thioether bond. Interestingly, Compound 1 exhibited a relatively selective growth inhibition against methicillin-resistant Staphylococcus aureus (MRSA) with the minimal inhibitory concentration (MIC) value of 8 mu g/mL.