Discovery And Biosynthesis Of Active Natural Products From The Sand-Fixing Plant Artemisia Desertorum Spreng.Syst.Veg.and Streptomyces Achromophilus

This paper includes two research projects,the first project is the study of the natural products of the sand fixing plant Artemisia desertorum Spreng.Syst.Veg.Artemisia desertorum Spreng.Syst.Veg.is a perennial herb of the genus Artemisia in the tube subfamily Carduoideae of the Compositae family.It has developed roots,strong environmental tolerance and creeping growth.In China,it is mainly grown in the desert and semi-desert areas of northwest,North China and northeast China for wind prevention and sand fixation.It can be used as traditional Chinese medicine to relieve cough,expectorate phlegm and relieve asthma.It can also be used to treat chronic bronchitis,asthma,cold,rheumatoid arthritis and other diseases.At the same time,studies have shown that its pollen can cause severe allergic reactions,leading to rhinitis.Besides,it has been reported to have anti-depressant properties.Previously,researchers had isolated the antimalarial drug artemisinin from Artemisia annua.Various studies show that Artemisia of Compositae is an important drug resource pool.Therefore,in this study,we tried to analyze the small molecules from natural components of Artemisia desterorum Spreng.Syst.Veg,separate the compounds in its petroleum ether extraction.The cold-maceration extraction method was used with 95%ethyl alcohol-water（Et OH-H₂O）solvent,and the crude extracts were obtained by concentration.The extracts were then extracted with petroleum ether,dichloromethane and ethyl acetate,Three components were obtained.The petroleum ether extracts were separated and purified by Sephadex LH-20 gel chromatography,silica gel chromatography,ODS chromatography and semi-preparable high performance liquid chromatography.A total of 16 compounds were isolated.According to the nuclear magnetic resonance spectrum and MS data,we identified the structure.The second project is the Discovery and biosynthesis of bioactive natural products from S.achromogenes.Polyene macrolides are used as antifungal drugs in clinic,which have good inhibitory effect on a variety of fungi.However,these compounds have strong renal toxicity,poor solubility and poor oral absorption.At the same time,with the increase of clinical drug demand,new antifungal prodrugs are needed.We found that the Streptomyces achromogenes var.streptozoticus NRRL3125 had inhibitory effect on fungi infected in the culture medium,and it was speculated that might have the ability to produce secondary metabolites of antifungal.After that,the compound was isolated and identified as a new polyene macrolide antibiotic.Genome sequence analysis revealed a biosynthetic gene cluster similar to lucensomycin.It has an unusual D-perosamine glycosyl substitution.Its gene cluster contains two P450 enzymes genes and one glycosyltransferase gene.D-perosamine synthesis related proteins were expressed in vitro and their activity was determined.And P450 gene deletion strainsΔluc6 andΔluc10were constructed,and new compounds were detected.