Abstract
Streptomyces species are ubiquitous, Gram-positive, spore-forming bacteria with the ability to produce various clinically relevant compounds. The strain 4503 T was isolated from mangrove sediments, showing morphological and chemical properties which were consistent with those of members of the genus Streptomyces. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolate was primarily identified as members of the genus Streptomyces, sharing more than 99% sequence identity to Streptomyces yatensis DSM 41771 T, S. antimycoticus NBRC 12839 T, and S. melanosporofaciens NBRC 13061 T. Average nucleotide identities (ANI) and digital DNA-DNA hybridization (dDDH) values between strain 4503 T and its close relatives were all below 95-96% and 75% of the novel species threshold, respectively. Results from phylogenetic, genomic, phenotypic, and chemotaxonomic characteristics analyses confirmed that the isolate represented a novel species of the genus Streptomyces, for which the name Streptomyces niphimycinicus sp. nov. 4503 T (= MCCC 1K04557T = JCM 34996 T) is proposed. The bioassay-guided fractionation of the extract of strain 4503 T resulted in the isolation of a known compound niphimycin C, which showed cytotoxic activity against nasopharyngeal carcinoma (NPC) cell lines TW03 and 5-8F with half maximal inhibitory concentration (IC50) values of 12.24 µg/mL and 9.44 µg/mL, respectively. Further experiments revealed that niphimycin C not only exhibited the capacity of anti-proliferation, anti-metastasis, induction of cell cycle arrest, and apoptosis, but was also able to increase the reactive oxygen species (ROS) production and regulate several signaling pathways in NPC cells. KEY POINTS: • Strain 4503 T was classified as a novel species of Streptomyces. • Niphimycin C correlates with the cytotoxic effect of strain 4503 T against NPC cells. • Niphimycin C induces apoptosis, autophagic flux disruption and cell cycle arrest.