Isolation And Biosynthesis Of Peptides And Polyketides Natural Products

According to statistics,more than 40%of clinical drugs are directly or indirectly derived from natural products,and more than 70%of the anti-infective drugs currently used clinically are derived from microbial natural products.In addition to the pharmaceutical industry,natural products have also been widely used in agriculture,animal husbandry and aquaculture,and have achieved significant benefits.In this thesis,two strains of actinomycetes were optimized and screened,and a series of studies on their secondary metabolites were conducted.Twenty-three natural products were isolated by TLC,silica gel column,ODS reversed-phase column,Sephadex LH-20,HPLC and other separation techniques,using a variety of spectroscopic techniques(HR-ESI-MS,1H NMR,13C NMR,HMQC 1H-1H COSY,HMBC,NOESY,IR)and other technologies identified the structure of the isolated compounds,including 17 new compounds.The preliminary antibacterial and cytotoxic activity assays.The specific results are as follows:The Streptomyces sp.120454 was fermented on a scale,and seven new non-ribosomal peptides(1-7),a new polyketide(8)and a new ?-lactone compound(16)and its ring-opening derivative(14)and(15).The absolute configuration of compound 1-7 was determined by the Marfey reaction.To study the biosynthesis pathway of ?-lactone compounds,we performed gene knock-out experiment and isolated a series of intermediates from their mutant strains.Streptomyces sp.ATCC 53653 was fermented which led to the isolation of two polyene natural products(10)and(11),and one terphenyl compound(13).Antibacterial assay showed that the peptide compounds 1-7 had weak cytotoxic activities,and the polyketides(8)and(9)had better antibacterial activities against Micrococcus luteus with a MIC of 2.0 and 8 uM.In addition,the biological activity,structure and biosynthesis of natural peptides produced by microorganisms were reviewed.