<i>Streptomyces griseus</i> KJ623766: A Natural Producer of Two Anthracycline Cytotoxic Metabolites β- and γ-Rhodomycinone

• Main Authors: Ahmed S. Abu Zaid, Ahmed E. Aleissawy, Ibrahim S. Yahia, Mahmoud A. Yassien, Nadia A. Hassouna, Khaled M. Aboshanab
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Molecules
• Subjects: cytotoxic activity; fermentation; <i>Streptomyces griseus</i>; β-rhodomycinone; γ-rhodomycinone
• Online Access: https://www.mdpi.com/1420-3049/26/13/4009

Background: This study aimed to produce, purify, structurally elucidate, and explore the biological activities of metabolites produced by <i>Streptomyces (S.) griseus</i> isolate KJ623766, a recovered soil bacterium previously screened in our lab that showed promising cytotoxic activities against various cancer cell lines. Methods: Production of cytotoxic metabolites from <i>S. griseus</i> isolate KJ623766 was carried out in a 14L laboratory fermenter under specified optimum conditions. Using a 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium-bromide assay, the cytotoxic activity of the ethyl acetate extract against <i>Caco</i>2 and <i>Hela</i> cancer cell lines was determined. Bioassay-guided fractionation of the ethyl acetate extract using different chromatographic techniques was used for cytotoxic metabolite purification. Chemical structures of the purified metabolites were identified using mass, 1D, and 2D NMR spectroscopic analysis. Results: Bioassay-guided fractionation of the ethyl acetate extract led to the purification of two cytotoxic metabolites, R1 and R2, of reproducible amounts of 5 and 1.5 mg/L, respectively. The structures of R1 and R2 metabolites were identified as β- and γ-rhodomycinone with CD₅₀ of 6.3, 9.45, 64.8 and 9.11, 9.35, 67.3 µg/mL against <i>Caco</i>2, <i>Hela</i> and <i>Vero</i> cell lines, respectively. Values were comparable to those of the positive control doxorubicin. Conclusions: This is the first report about the production of β- and γ-rhodomycinone, two important scaffolds for synthesis of anticancer drugs, from <i>S. griseus</i>.