Study On Secondary Metabolites With Antibiotic Activities Of Deep Marine-Derived Streptomyces Sp. OUCMDZ-4112

Marine with especial surroundings of high pressure, high salinity, low temperature, low nutrition and low illumination, contain a huge resource of microorganism, which have unique metabolic mechanism different from metabolic mechanism of terrestrial microbes. The majority of secondary metabolites derived from marine microbes mostly possess novel chemical structure and diverse antibiotic activities, such as antitumor activity, antibacterial activities, anti-inflammatory activity, et al. It make them play a important role in exploitation of new drug. Unto 2013, we already have had seven marine-derived drug in market approved by FDA or EMEA, eight marine-derived compounds in clinic trial phase, and eighteen marine-derived compounds been quit in clinic trial phase. One of those drug or lead compound is an anticarcinogen, Marizomib obtained from a marine actinomycete, and other one is an anticarcinogen, Plinabulin obtained from a marine fungi. Such abundant resource of marine microorganism and various bioactive activities of secondary metabolites of marine-derived microorganism show a big latent capacity in discovery of new drug.In order to discover novel chemical structure or possessed-by bioactive compounds from microbes, many strains isolated from samples of marine sediments derived from the South China Sea have been screened by a compositive method including chemical screening and bioactive screening. The chemical screening is focus on the diversity, novelty and amount of the secondary metabolites, in which TLC and HPLC-UV were used. Meanwhile, the bioactive screening focus on antimicrobial activities or cytotoxic activities of the secondary metabolites. We choose MCF-7 tumor cell lines as cytotoxic model, and Staphylococcus aureus, Candida albicans and other pathogenic as antimicrobial model in screening. By the comprehensive analysis of the chemical and biological results, one strain has been selected for further study.Firstly, zymolytic conditions of target strain, like medium, time, temperature, salinity and so on have been optimized by compositive screening method, for the optimal one. We finally contain over 100g extract from the broth of first-time and second-time large-scale fermentation of the target actinomycete. Dependent on extensive column chromatography and HPLC, we separated pure compounds from the extract. All about fifteen compounds have been isolated from stremptomyces sp. OUCMDZ-4112.By means of modern spectral analysis(NMR, MS, CD, UV, IR), X-ray and chemical methods the structures of fifteen compounds have been determined. Among them, 14 is a new prodigiosin-like compound and 1 and 2 are known prodigiosin-like compounds,3-1 and 3-2 are a pair of new enantiomer, others are known compounds and one undecided compound.Three kinds of bioactive activities of these compounds have been evaluated, including antimicrobial activities, antitumor activities and α-glycosidase inhibitory activity. Compound 1 and 2 show potent cytotoxic activity against K562 cell lines, with IC50 value of 0.60 and 0.01μM. Moreover these two compounds show significant cytotoxic activities against MCF-7 and A549, as literatures said. Compound 1 and 2 also demonstrates a comparativeα-glycosidase inhibitory activity as positive drug, with IC50 0.082 and 0.92 mM. The pair of enantiomer haven’t show any bioactive activities.