Chemical study of the insect-derived bacterium, Streptomyces sp. NA4286, led to the discovery of four new polyketides, murayaquinones B-E (1–4), together with a known compound, murayaquinone (5). The structures of new compounds (1–4) were determined by extensive analysis of their NMR and HRESIMS data. The absolute configuration of (+)-1 and ()-1 was assigned through comparison of experimental and calculated ECD spectra. Murayaquinone D (3) exhibited potent cytotoxic activities against six human cancer cell lines with IC50 values ranging from 1.03 to 9.99 lM.