A marine-derived actinobacteria Streptomyces sp. M10 was identified as a prolific antifungal compounds producer and shared a 99.02 % 16S ribosomal RNA (rRNA) sequence similarity with that of Streptomyces marokkonensis Ap1(T), which can produce polyene macrolides. To further evaluate its biosynthetic potential, the 7,207,169 bp Streptomyces sp. M10 linear chromosome was sequenced and mined for identifiable secondary metabolite-associated gene clusters. A total of 20 secondary metabolite-associated gene clusters were deduced, including three polyketide synthases (PKSs), four non-ribosomal peptide synthetases (NRPSs), four hybrid NRPS-PKSs, three NRPS-independent siderophores, and two lantibiotic and four terpene biosynthetic gene clusters. One of the type I PKS gene cluster, pks1, shared a 85 % nucleotide similarity with candicidin/FR008 gene cluster, indicating the capacity of this organism to produce polyene macrolides. This assumption was verified by a scale-up culturing of Streptomyces sp. M10 on A1 agar plates, which lead to the isolation of two polyene families PF1 and PF2, with characteristic UV adsorption at 269, 278, and 290 nm (PF1) and 363, 386, and 408 nm (PF2), respectively. Compound 9-04 was further purified from PF1, and its chemical structure was partially elucidated to be a typical polyene macrolide by NMR and UV spectrum. This study affirmatively identified Streptomyces sp. M10 as a source of polyene metabolites and highlighted genome mining of interested organism as a powerful tool for natural product discovery.