Study On Secondary Metabolites From Streptomyces Xinghaiensis NRRL B24674~T

Microbes is an impotant source of natural products,and provides an important basis for the development of new drugs.With the depth of the research,reseachers not only pay attention to terrestrial microorganisms,but also the microorganisms from the ocean and other special habitats such as acidic or alkaline conditions,and conditions with high or low temperature.In this study,we carried out the isolation and identification of the secondary metabolites of Streptomyces xinghaiensis NRRL B24674~T,which was isolated from Xinghai Bay in Dalian.After the fermentation conditions were optimized,a large scale fermentation(85 L)was performed.The secondary metabolites were purified by using different chromatography techniques including thin layer chromatography(TLC),normal and reversed phase silica gel column chromatography,sephadex LH-20 column chromatography and high performance liquid chromatography.Finally,13 compounds were purified.Among them,the structures of 11 compounds were elucidated by mass spectroscopies(MS)and nuclear magnetic resonance spectroscopies(NMR).Compounds were identified as:xiamycin(1);19-hydroxyl-xiamycin(2);N-methanesulfonyl-xiamycin(3);oxiamycin(4);19-methanesulfinic acid-21-hydroxyl-xiamycin ester(5);19-carbonyl-xiamycin(6);19-methoxyl-xiamycin(7);N-C~7-dixiamycin(8);19-hydroxyl-24-methylester-N-N-dixiamycin(11);N-N-dixiamycin(12/13).Structures of compound 9 and 10 were not elucidated due to the small amount.Among them,compound 8 exhibited potency against Bacillus mycoids with the MIC value of 2.5?M.In addition,2-methylthio-N~6-(4-hydroxyisopentenyl)-adenosine was purified from the fermentation crude extract by genome mining.It is the first time to identify 2-methylthio-N~6-(4-hydroxyisopentenyl)-adenosine from Streptomyces.We assumed that this compound probably derived from the modification of tRNA according to the literatures.The identification of multiple new secondary metabolites from the marine-derived S.xinghaiensis NRRL B24674~T revealed that the bacteria can produce structurally diverse natural products.In particular,the identification of seven new xiamycin analogues not only set the stages for xiamycin biosynthetic studies,but also enriched the natural product libraries for the drug development and application of microbial resources.