This study performed an optimization of the fermentation conditions to activate the expression of the zunyimycin family biosynthesis genes of the zunyimycin-producing streptomycetes strain Streptomyces sp. FJS31-2. Bioassay-guided isolation and purification by varied chromatographic methods yielded two new compounds of the zunyimycin derivatives, namely, 31-2-7 and 31-2-8, accompanied with three known anthrabenzoxocinones family members of zunyimycin A, BE24566B, and chloroanthrabenzoxocinone. Their structures were elucidated by NMR, HRESIMS, IR, UV, and CD. Results showed that these two compounds were structurally similar to the previously reported compound zunyimycin A but differed in positions and number of chlorine atom substitution. The two novel compounds were called zunyimycins B and C. Antibacterial activity assay indicated that zunyimycin C showed a good inhibitory effect on the methicillin-resistant Staphylococcus aureus and Enterococci.

Genome mining is an effective tool used to discover novel natural products from actinomycetes. Genome sequence analysis of Streptomyces sp. FJS31-2 revealed the presence of one putative type II polyketide gene cluster (ABX), which may correspond to type II polyketide products including BE-24566B and its chloro-derivatives. The addition of natural humus acid successfully activated the biosynthsis of the abx gene cluster. BE-24566B and its chloro-derivatives, named zunyimycin A, were also detected. The targeted deletion of the polyketide skeleton synthesis genes such as abxp, abxk, and abxs was performed in the wild strain to identify the gene cluster for BE-24566B biosynthesis.

The present study examined differential expression levels of DNA damage repair genes in COLO 205 colorectal cancer cells, with the aim of identifying novel biomarkers for the molecular diagnosis and treatment of colorectal cancer. COLO 205-derived cell spheres were cultured in serum-free medium supplemented with cell factors, and CD133+/CD133− cells were subsequently sorted using an indirect CD133 microbead kit. In vitro differentiation and tumorigenicity assays in BABA/c nude mice were performed to determine whether the CD133+ cells also possessed stem cell characteristics, in addition to the COLO 205 and CD133− cells. RNA sequencing was employed for the analysis of differential gene expression levels at the mRNA level, which was determined using reverse transcription-quantitative polymerase chain reaction. The mRNA expression levels of 43 genes varied in all three types of colon cancer cells (false discovery rate ≤0.05; fold change ≥2). Of these 43 genes, 30 were differentially expressed (8 upregulated and 22 downregulated) in the COLO 205 cells, as compared with the CD133− cells, and 6 genes (all downregulated) were differentially expressed in the COLO 205 cells, as compared with CD133+ cells. A total of 18 genes (10 upregulated and 8 downregulated) were differentially expressed in the CD133− cells, as compared with the CD133+ cells. By contrast, 6 genes were downregulated and none were upregulated in the CD133+ cells compared with the COLO 205 cells. These findings suggest that CD133+ cells may possess the same DNA repair capacity as COLO 205 cells. Heterogeneity in the expression profile of DNA damage repair genes was observed in COLO 205 cells, and COLO 205-derived CD133− cells and CD133+ cells may therefore provide a reference for molecular diagnosis, therapeutic target selection and determination of the treatment and prognosis for colorectal cancer.