Brocaeloid D,a novel compound isolated from a wheat pathogenic fungus, Microdochium majus 99049

Microbes serve as the most important resource for drug discovery.During our screening for bioactive compounds from our natural products library,a pathogenic fungus,Microdochium majus strain 99049,from wheat was selected for further investigation.A new alkaloid named brocaeloid D(1),together with six previously characterized compounds(2–7)were identified.Compound 1 belongs to 4-oxoquinoline with C-2 reversed prenylation and a succinimide substructure.All the structures of these newly isolated compounds were determined by different means in spectroscopic experiments.The absolute configurations of 1 was further deduced from comparison of its CD spectrum with that of known compound 2.The bioactivities of these identified compounds were evaluated against several pathogenic microorganisms and cancer cell lines.Compounds 1–5 showed activity against HUH-7 human hepatoma cells with IC50 values of 80μg/mL.Compound 6 showed mild activity against HeLa cells(IC50=51.9μg/mL),weak anti-MTB activity(MIC=80μg/mL),and moderate anti-MRSA activity(MIC=25μg/mL),and compound 7 showed weak anti-MRSA activity(MIC=100μg/mL).

Discovery of tanshinone derivatives with anti-MRSA activity via targeted bio-transformation

Two potent anti-MRSA tanshinone glycosides(1 and 2)were discovered by targeted microbial biotransformation,along with rapid identification via MS/MS networking.Serial reactions including dehydrogenation,demethylations,reduction,glycosylation and methylation have been observed after incubation of tanshinone IIA and fungus Mucor rouxianus AS 3.3447.In addition,tanshinosides B(2)showed potent activities against serial clinical isolates of oxacillin-resistant Staphylococcus aureus with MIC values of 0.78 mg/mL.This is the first study that shows a significant increase in the level and activities of tanshinone glycosides relative to the substrate tanshinone IIA.

A systems approach using OSMAC,Log P and NMR fingerprinting:An approach to novelty

The growing number of sequenced microbial genomes has revealed a remarkably large number of secondary metabolite biosynthetic clusters for which the compounds are still unknown.The aim of the present work was to apply a strategy to detect newly induced natural products by cultivating microorganisms in different fermentation conditions.The metabolomic analysis of 4160 fractions generated from 13 actinomycetes under 32 different culture conditions was carried out by 1H NMR spectroscopy and multivariate analysis.The principal component analysis(PCA)of the 1H NMR spectra showed a clear discrimination between those samples within PC1 and PC2.The fractions with induced metabolites that are only produced under specific growth conditions was identified by PCA analysis.This method allows an efficient differentiation within a large dataset with only one fractionation step.This work demonstrates the potential of NMR spectroscopy in combination with metabolomic data analysis for the screening of large sets of fractions.