Research On Secondary Metabolites From Streptomyces Sp.NAK2211 And Chaetomium Globosum CBX148.51

Microbial secondary metabolites with diverse structures and pronounced biological activities have historically served as significant sources for drug leads.However,due to the limitation and repeatable exploration of normal soil microorganism,the probability of discovery of novel bioactive natural products has dramatically decreased.Microorganisms,who is long-term survival in the extreme environment such as high pressure,high salinity,low temperature,and eutrophication,may have a special response mechanism to special environments to produce new secondary metabolites that are different from conventional soil microorganisms.In view of this,it has become a research hotspot in the study of natural products in recent years to explore the relatively weak research on special environment microbes.In this thesis,more than 300 microorganisms were screened and two of them were identified for large scale fermentation.Various tools like silica gel column chromatography,gel column chromatography,MPLC(medium pressure liquid chromatography),HPLC(high performance liquid chromatography)were used to separate the crude extract of fermentation.A total of 20 compounds were obtained,16 of them were found as new and their structures were elucidated by extensive analysis of spectroscopic data such as LCMS,1D and 2D NMR.The results were described as follows:Part 1: Two cinnamic acid-containing non-ribosomal peptides,including a new compound pepticinnamin N(1)and a recently reported compound pepticinnamin H(2),were isolated from the large-scale fermentation broth of Streptomyces sp.NAK2211,their structures were identified by subsequent analysis of NMR and gene cluster.Through literature search and bioinformatics analysis,we proposed the biosynthetic pathway of compound 1.In addition,three new amtromycin(3-5)were isolated from the fermentation broth too.Part 2: A series of azaphilones(7-20)natural products were isolated from the large-scale fermentation of Chaetomium globosum CBS148.51 in rice medium.Their planar structures were elucidated by mass spectrometry and NMR data analysis.Twelve compounds have not been reported,including reduced azaphilone dimer and modified azaphilone monomers,which enriches the structural diversity of these natural products.Sixteen new compounds were separated from the fermentation of special eco-environment microorganisms,which indicated that special eco-environment microorganisms can produce more new natural products than normal microorganisms.In addition,this article reviews the structural features and biosynthesis research progress of the cinnamic acid-containing non-ribosomal peptides.