Identification Of The Secondary Metabolites From Streptomyces Sp. CPCC 202369 And Streptomyces Sp. CPCC 205159

Objective: Actinomycetes are well known for their ability to produce secondary metabolites with diverse structures and bioactivities.Especially,Streptomyces as a genus of actinomycetes is the most important producing organism of microbial pharmaceuticals so far used clinically.In our previous study,dozens of unidentified Streptomyces strains had been screened for their antibacterial activity.Among them,two(Streptomyces sp.CPCC 202369 and Streptomyces sp.CPCC 205159)were selected due to their significant antibacterial activity,and were chosen in this study for a further investigation of the bioactive secondary metabolites produced by them.Methods: Streptomyces sp.CPCC 202369 and Streptomyces sp.CPCC 205159 were grown on ISP2 or A2 agar plates for solid-state fermentation.The agar cultures were extracted with ethyl acetate(EA).The EA layer was concentrated to obtain the crude extracts.A combination of ODS flash chromatography,Sephadex LH-20 column chromatography and semi-preparative high performance liquid chromatography was established to isolate secondary metabolites from the extracts.The structures of these secondary metabolites(compounds)were elucidated by comprehensive analysis of their LC-MS and NMR data.Their antibacterial activities were also assayed or determined by broth microdilution method.Results: Eleven compounds were obtained from Streptomyces sp.CPCC 202369,including five new compounds 202369-A(3),202369-B1(8),202369-B2(9),202369-C1(10)and 202369-C2(11),and six known compounds X-14881A(1),fujianmycin A(2),fridamycin E(4),tetrangomycin(5),deoxytetrangomycin(6),and rubiginone B2(7).Compounds 1,2,5-7,10 and 11 belong to classical angucyclines,while compounds 3,4,8 and 9 are rearranged angucyclines.Compounds 2,8 and 10 displayed moderate activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus(MRSA)(MIC 3.13-100 μM).However,compound 202369-A(3)showed no activity against the above test strains.Two known compounds geldanamycin(12)and 17-Odemethylgeldanamycin(13)were obtained from Streptomyces sp.CPCC 205159.There are some other secondary metabolites produced by the strain,and they will be identified in the future.Conclusion: There are compounds with novel chemical structures and biological activities in the secondary metabolites of Streptomyces sp.CPCC 202369 and Streptomyces sp.CPCC 205159.So natural products from microorganisms are still an important field in the research of new drugs.