Studies On The Secondary Metabolite From Two Strains Of Deep Soil Streptomyces

Streptomyces is a Gram-positive actinomycetes, can produce a large number ofactive secondary metabolites, many of which have entered clinical application, suchas streptomycin, kanamycin, erythromycin, etc. Research on streptomyces is of greatsignificance for the discovery of new drugs or lead compounds. This paper adopt aintegrated method including biology and chemistry to screen25streptomyces whichderived from the deep soils collected from Qingdao subway investigation wells, andthen we got two talent streptomyces. We carried out in-depth study about these twostreptomyces, including isolation and screening of Streptomyces, optimization offermentation conditions, the separation of the monosomic compounds, the structuralidentification of the compounds, and the biological activity evalution of compounds.25streptomyces were isolated from the three pieces of deep soil samplescollected from the Qingdao subway investigation well. By the combination screeningmethods of TLC-HPLC-UV-cytotoxic activity, we got two talent streptomyce strainsas our study object.80L-scale fermentation broth of the Streptomyces sp. QD01-1and110L-scale fermentation broth of the Streptomycetes sp. QD01-2were performed toobtain the active extracts，respectively. By means of chromatography over silica gelcolumn, Sephadex LH20, preparative TLC and semi-preparative HPLC, seven (1-7)and ten compounds (8-17) were isolated from Streptomyces sp. QD01-1andStreptomyces sp. QD01-2, respectively.Basing on their physico-chemical properties and spectral data (IR, UV, MS,NMR, CD and X-ray etc.), seventeen compounds were identified. Among them eightcompounds are new compounds, including seven amino-imidazoles and onegilvocarcins glycoside whose absolute configuration was determined by X-ray andCD analysis. The chemical structure types of the known compounds were involvedfour benzene derivatives, three gilvocarcins glycosides, two cyclic peptides and onethio-compound. Cytotoxic activities of four compounds (8-11) against several cancer cell lineswere assayed by MTT method, among them compound11showed good cytotoxicityagainst P388、MCF-7and K562with IC501.1μM、1.8μM、0.8μM, respectively.The anti-bacterial activities were tested by drug sensitive slips method anddouble dilution. These four gilvocarcin glycosides displayed good anti-bacterialactivities. We also summarize the simple structure-activity relationship of these fourgilvocarcin glycosides by our test results and the related references.Summarily, this work obtained two talent strains from23candidate streptomycesstrains and17compounds were isolated. Among them7compound were newcompounds and4compounds displayed good biological activity. This work hasenriched natural products and paved a way for the future research.