The Active Metabolites From Two Endophytes Based On The OSMAC Strategy

After many years of research,the study of secondary metabolites from endophytes has produced chemical diversity and bioactivity.So the production of new bioactive compounds has a great prospect in pharmaceutical research.Modern genomic sequencing technology show that not all gene clusters are expressed regularly under conventional growth conditions.To further expand the chemical diversity of metabolites from individual strains,"one strain-many compounds(OSMAC)" strategy can be used to the studies of active compounds from endophytes.The thesis is divided into three chapters:The first chapter was mainly about the progress on secondary metabolites of endophytic fungi based on OSMAC strategy.In this review,various medium conditions and gene screening have been successfully applied to the research of metabolites and biosynthesis from microbe,And the study can lead to the chemical diversity of secondary metabolites.The second chapter was mainly about the secondary metabolite and its bioactivity of Chatomium globosum YNH-16,isolated from the aquatic plant,Hydrocharis dubia in Lijiang,Yunnan province,China.The strain was fermented on Chinese yam medium,based on the OSMAC strategy.Thirteen compounds were isolated and identified from the Chatomium globosum YNH-16.Including two new compounds: 10,11-dihydroxylaureonitol(1)and yamchaetoglobosin A(2),and eleven known compounds: ergos-terolperoxide(3),cerebrosides C(4),adenosine(5),uridine(6),aureonitol(7),orsellinic acid(8),orcinol(9),2-hydroxybenzoic acid(10),2-hydroxy phenyl acetic(11),tyrosol(12),styrene glycol(13).Compound 2 showed obvious nitric oxide(NO)inhibitory activity(inhibition rate at 92.51 ± 1.10 %),and an inhibitory activity on AChE(inhibition rate at 38.20 %)at 50 ?M.Compound 2 had strong inhibitory activity on leukemic HL-60 cell line(inhibition rate at 96.22 %)at 40 ?M.Compounds 1,and 2 had anticoagulant effect with prothrombin time(PT)at 16.8s.The third chapter was mainly about the secondary metabolites and their activities of Stachybotrys sp.,isolated from soil samples of Tibetan plateau.The TLC screening was applied to the medium optimization(different medium: 2 % acetic acid,yam,Codonopsis blleyana,Smallanthus sonchifolius,Czapek–Dox,improved Martin,and rice solid medium).After screening,the selective fungus was fermented on the solid medium of rice.Twelve compounds were isolated and identified from the.Stachybotrys sp.Including two new compounds: bisabosqual E(1),bisabosqual F(2),and ten known compounds: 2-hydroxybenzaldehyde(3),ergosterol(4),trans-so-brerol(5),1?,4?,7?-trihydroxyeudesmane(6),sterigmatocystin(7),averufin(8),(22E,24R)-ergosta-7,22-diene-3?,5?,6?-triol(9),5,6-epoxy-22-en-3-ol-ergosterol(10),stachybotrylactam(11),and stachybotramide(12).Compounds 1,2 had the inhibitory activity of nitric oxide(NO)formation(the inhibitory rate at 47.59 ± 3.18 %,22.68 ± 2.84 %)at 50 ?M.Compounds 1 and 2 were screened for anti-tumor cytotoxicity at the concentration of 40 ?M,compound 1 had a cetain inhibitory activity on leukemia HL-604 and breast cancer MCF-7(the inhibitory rates at 38.20 % and 49.02 %).Compound 2 has weak inhibitory activity against breast cancer MCF-7(inhibition at 33.20 %).Compound 1 had anticoagulant effect with activated partial thromboplastin time(APTT)at 32.1 ±0.17 s.Thees results show that the OSMAC can be applied to the discovery of novel compounds from endophytic fungi.In this experiment,the different metabolites were obtained from fungi by changing the medium.The metabolites can provide a basis on the discovery of new drugs.