Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, China.
Appl Microbiol Biotechnol. 2023 Oct;107(20):6325-6338. doi: 10.1007/s00253-023-12707-w. Epub 2023 Aug 11.
Streptomyces species are ubiquitous, Gram-positive, spore-forming bacteria with the ability to produce various clinically relevant compounds. The strain 4503 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, S. antimycoticus NBRC 12839, and S. melanosporofaciens NBRC 13061. Average nucleotide identities (ANI) and digital DNA-DNA hybridization (dDDH) values between strain 4503 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 (= MCCC 1K04557 = JCM 34996) is proposed. The bioassay-guided fractionation of the extract of strain 4503 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 (IC) 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 was classified as a novel species of Streptomyces. • Niphimycin C correlates with the cytotoxic effect of strain 4503 against NPC cells. • Niphimycin C induces apoptosis, autophagic flux disruption and cell cycle arrest.
链霉菌属是普遍存在的革兰氏阳性、产孢子细菌，具有产生各种临床相关化合物的能力。菌株 4503 从红树林沉积物中分离出来，其形态学和化学性质与链霉菌属的成员一致。基于 16S rRNA 基因序列的系统发育分析表明，该分离株主要被鉴定为链霉菌属的成员，与链霉菌属的 Streptomyces yatensis DSM 41771、Streptomyces antimycoticus NBRC 12839 和 Streptomyces melanosporofaciens NBRC 13061 的序列同一性超过 99%。菌株 4503 与其近亲之间的平均核苷酸同一性（ANI）和数字 DNA-DNA 杂交（dDDH）值均低于 95-96%和 75%的新种阈值。基于系统发育、基因组、表型和化学分类特征的分析结果证实，该分离株代表了链霉菌属的一个新种，因此将其命名为链霉菌属 niphimycinicus sp. nov. 4503（=MCCC 1K04557=JCM 34996）。生物活性导向的菌株 4503 提取物的分离得到了一个已知化合物 niphimycin C，它对鼻咽癌细胞系 TW03 和 5-8F 具有细胞毒性，半数最大抑制浓度（IC）值分别为 12.24μg/mL 和 9.44μg/mL。进一步的实验表明，niphimycin C 不仅具有抗增殖、抗转移、诱导细胞周期停滞和细胞凋亡的能力，还能够增加 NPC 细胞中的活性氧（ROS）产生并调节几种信号通路。关键要点：
菌株 4503 被分类为链霉菌属的一个新种。
Niphimycin C 与菌株 4503 对 NPC 细胞的细胞毒性作用相关。
Niphimycin C 诱导细胞凋亡、自噬通量破坏和细胞周期停滞。
