Studies On The New Cell Cycle Inhibitors Produced By Streptomyces Flavoretus 18522 And Streptomyces Pseudoverticillus YN17707

Total 280 strains of microorganisms (180 actinomycete and 100 fungal stains), which were isolated from the soil and plant samples collected in Xinjiang, Yunnan, Guizhou and North-east area, China, were subjected to the screening work for the cell cycle inhibiting and apoptosis inducing activities by the use of flow cytometry using tsFT210 cells, a mouse temperature sensitive cdc2 mutant cell line. These strains were fermented in four kinds of liquid media for actinomycetes and four kinds of liquid media for fungi, respectively, to obtain 1120 test samples. Through a preliminary screening with these test samples, total 56 strains (35 actinomycecte and 21 fungal strains) possessing 20% of the 280 strains were picked out, the samples from which showed to a certain extent the cell cycle inhibiting and/or apoptosis inducing activities in the preliminary screening. These 56 strains were re-fermented using the media selected from the preliminary experiment to obtain 280 test samples and in retesting with the 280 samples, 26 strains were found to be bioactive, including 20 actinomycete and 6 fungal strains. The 26 strains possessed 9.3% of the total 280 strains examined. In the third screening (stability- and solubility-tests for the bioactive components), the metabolites of 5 strains including 4 actinomycete and 1 fungal strains showed better stability and acceptable solubility in organic solvents. Among them, two actinomycete strains, 18522 and YN17707, which had stronger activity, were chosen as the aimed strains to investigate their bioactive metabolites in the present dissertation.The two aimed actinomycete strains, 18522 and YN17707, were identified as Streptomyces flavoretus 18522 and Streptomyces pseudoverticillus YN17707 respectively through taxonomic studies. Then the time course experiments for the fermentation of these two producing strains were carried out, followed by solvent extraction tests for the active components. On the basis of these experiments, large-scale fermentation and preparation of the active fractions were performed to obtain the active fractions of the two strains respectively. By activity-guided separation procedures, seven active compounds, 1-5, 10 and 11, and two pairs of cyclic dipeptides, 6/7 (1:2) and 8/9 (3:1), were obtained...