Research On Fungi Secondary Metabolite Diversity Induced By Oxidase Inhibitors

In this research,secondary metabolites by chemical induction from marine fungi and Myceliophthora thermophila were studied,oxidase inhibitors,apocynin for example,was used as induction reagent to activate the silent biosynthetic genes of fungi and produced varies new secondary metabolites.Firstly,we cultured these fungi in normal lab culture medium with addition of oxidase inhibitors.As a prelimitary screening procedure,we cultured eight fungi strains and tested three kinds of oxidase inhibitors.Finally we chose apocynin as the induction reagent for further study,as its induction rate was as high as 75%.Aspergillus sp.SCSIOW20?W20?and Myceliophthora thermophila?MT?were chosen for the following study,because their results were the best from all of the fungi strains.After large scale fermentation of the two strains,sephadex LH-20 and ODS-HPLC were mainly used to isolatethe differential metabolites from the intact and induced fungi fermentation extracts.As a result,22 metabolites?Comp.1-22?were purified,13 of which?Comp.1-13?were differential metabolites,9 of which were from Aspergillus sp.SCSIOW20,and 4 were from Myceliophthora thermophila.Four compounds were elucidated as new compounds,3 of which were classified as new yanuthone derivatives,and named as Yanuthone X₃,X_4,and X₅.Bioactivity of the isolated compounds were also studied.Comp.6 and 16 showed strong antioxidative activity with IC₅₀=8.55 and 4.43?M.Comp.2,6,7,9,16,17,and 19 showed antimicrobial activity against MASA.In this study,we also tried to explain how apocynin induced new secondary metabolites production by transcriptomics and metabonomics analysis.Differential expression analysis showed down-regulation of 48 genes and up-regulation of 22genes,and metabonomics analysis showed the variation of 44 primary metabolites.