Studies On Secondary Metabolites Of Streptomyces Malaysiensis And Their Biological Activities

Streptomyces is a very special genus of Gram-positive bacteria.Streptomyces has excellent activity because it is a strain with high Gluc C content in prokaryotes.so far,more than 7000 active compounds have been found in Streptomyces,of which more than 100 have been used in clinical drugs and agriculture and are of high research value.Streptomyces is a common secondary metabolite compound Ansamycin antibiotics.Studies have shown that it has good antibacterial,anti-tumor and immune activity.In this paper,Streptomyces malaysiensis DSM4137 strain was selected as the research object,the optimal medium was selected for fermentation,the secondary metabolites were separated by column chromatography,the structure was identified by pop analysis technology,and the activity of the identified structure was evaluated so as to provide a compound basis for the discovery of lead compounds.（1）Screening of fermentation medium:six media were selected to ferment DSM4137,and ethyl acetate was used to extract the fermentation product.The fermentation extract was evaluated by HPLC,anti-tumor and immune activity.The results showed that the chemical composition and activity evaluation of SFM medium were better than the other five media.HPLC patterns showed that there were a large number of absorption peaks of fermentation products 254 and 306nm in SFM medium,indicating that many ANSA mycin compounds were produced in SFM medium,which is the focus of this thesis.The evaluation of anti-tumor activity and immune activity was higher than that of the positive control,indicating that it contained compounds with good activity,and SFM medium was the most suitable for the fermentation culture of Streptomyces malaysiensis DSM4137.（2）Fermentation of Streptomyces malaysiensis DSM4137 and isolation and identification of fermentation products:30g of extract was obtained by massive fermentation of Streptomyces malaysiensis DSM4137 in SFM medium.The fermentation extract was isolated by TLC,CC column chromatography,Sephadex LH-20 dextran column chromatography,C18 column chromatography and semi-prepared HPLC.A total of 11 compounds were obtained,including 7 anisamycin compounds,2 polyether compounds,1 terpenoid compound and 1 ketone compound.（3）Bioactivity Evaluation of the secondary metabolites of Streptomyces DSM4137:the antitumor and immunological activities of the metabolites were studied.The results showed that compounds 1-4 had good antitumor and immunological activities.The antitumor activities of compounds 2 and 4 were 9.30,7.56,19.14 and 7.58μM,respectively,and the activities of compounds 2 and 4 were stronger than those of adriamycin hydrochloride(IC₅₀=8.48μM),and the immunoactivity of compounds IC₅₀were 9.30,7.56,19.14 and 7.58μM,respectively 1.05,0.40,2.62 and 1.84μMwere stronger than positive control Cs A(IC₅₀=2.82μM),which provided a compound basis for the development of antitumor and immune activities...