A fungus that grows on pinecones yields a compound with antifungal activity that has become the natural model for a significant innovation in crop protection. Variation and optimization of the lead structure of strobilurin A (1) and selection of derivatives which fulfill all practical requirements, for example, kresoxim-methyl (2), led to an exciting and pan-industrial competition for the development of the strobilurines as a new, highly active, and broadly applicable class of fungicides-a fascinating success story.

To date approximately 100 000 fungal species are known although far more than one million are expected. The variety of species and the diversity of their habitats, some of them less exploited, allow the conclusion that fungi continue to be a rich source of new metabolites. Besides the conventional fungal isolates, an increasing interest in endophytic and in marine-derived fungi has been noticed. In addition new screening strategies based on innovative chemical, biological, and genetic approaches have led to novel fungal metabolites in recent years. The present review focuses on new fungal natural products published from 2009 to 2013 highlighting the originality of the structures and their biological potential. Furthermore synthetic products based on fungal metabolites as well as new developments in the uses or the biological activity of known compounds or new derivatives are discussed.

The strobilurins are two antifungal antibiotics which were isolated from the mycelium of Strobilurus tenacellus strain No. 21602. The strobilurins A and B are highly active against yeasts and filamentous fungi. In vitro antitumor activity was tested using cells of the ascitic form of EHRLICH carcinoma.The strobilurins strongly inhibited the incorporation of radioactive leucine, uridine, and thymidine into the acid-insoluble fraction of cells (protein, RNA, and DNA). The molecular formulas as determined by high resolution mass spectrometry are C,6H,603 for strobilurin A and C17H19ClO4 for strobilurin B. The basidiomyceteStrobilurus tenacellus is a small agaric growing on decaying cones of Purus silverstris.Cultures of this species growing on agar plates or in submerged culture show marked antifungal activity. From the mycelium of Strobilurus tenacellus strain No. 21602 we have isolated two antibiotics which have been named strobilurins A and B. In the following paper we wish to report the fermentative production, the isolation, and the chemical and biological characterization of the strobilurins. The determination of the structure will be subject of a second publication. FermentationStrobilurus tenacellus 21602 was maintained on agar slants of a yeast extract-malt extract (YM) medium (4g yeast extract, 4 g glucose, 10 g malt extract per liter). For submerged cultivation a 150 ml of YM medium was inoculated with mycelium from one agar slant and incubated for 5 days on a rotary shaker at 22°C and 120 rpm. This culture was used to inoculate 10 liters of the same medium in a New Brunswick FS 314 fermentation apparatus. One ml of polyol antifoam was added initially, and the mycelia were grown at 22°C with mechanical stirring (150 rpm), and an aeration rate of 2 liters air/min. IsolationThe mycelia from a 10-liter culture grown for 4 days were collected on a Buchner funnel, and washed several times with water. The cells (wet weight 210 g) were extracted first with 600 ml of methanolacetone (2: 1), and then with 700 ml of methanol. The combined extracts were evaporated and the antibiotics were extracted with 100 ml of chloroform from the residue. The chloroform was dried over anhydrous Na2SO4 and evaporated yielding 3.1 g of a dark brown oil. The crude extract was

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Apples (Malus spp., Rosaceae) and products thereof contain high amounts of polyphenols which show diverse biological activities and may contribute to beneficial health effects, like protecting the intestine against inflammation initiated by chronic inflammatory bowel diseases (IBD). IBD are characterized by an excessive release of several proinflammatory cytokines and chemokines by different cell types which results consequently in an increased inflammatory response. In the present study we investigated the preventive effectiveness of polyphenolic juice extracts and single major constituents on inflammatory gene expression in immunorelevant human cell lines (DLD-1, T84, MonoMac6, Jurkat) induced with specific stimuli. Besides the influence on proinflammatory gene expression, the effect on NF-kappaB-, IP-10-, IL-8-promoter-, STAT1-dependent signal transduction, and the relative protein levels of multiple released cytokines and chemokines were studied. DNA microarray analysis of several genes known to be strongly regulated during gastrointestinal inflammation, combined with quantitative real-time PCR (qRT-PCR) revealed that the apple juice extract AE04 (100-200 microg/mL) significantly inhibited the expression of NF-kappaB regulated proinflammatory genes (TNF-alpha, IL-1beta, CXCL9, CXCL10), inflammatory relevant enzymes (COX-2, CYP3A4), and transcription factors (STAT1, IRF1) in LPS/IFN-gamma stimulated MonoMac6 cells without significant effects on the expression of house-keeping genes. A screening of some major compounds of AE04 revealed that the flavan-3-ol dimer procyanidin B(2 )is mainly responsible for the anti-inflammatory activity of AE04. Furthermore, the dihydrochalcone aglycone phloretin and the dimeric flavan-3-ol procyanidin B(1 )significantly inhibited proinflammatory gene expression and repressed NF-kappaB-, IP-10-, IL-8-promoter-, and STAT1-dependent signal transduction in a dose-dependent manner. The influence on proinflammatory gene expression by the applied polyphenols thereby strongly correlated with the increased protein levels investigated by human cytokine array studies. In summary, we evaluated selected compounds responsible for the anti-inflammatory activity of AE04. In particular, procyanidin B(1), procyanidin B(2), and phloretin revealed anti-inflammatory activities in vitro and therefore may serve as transcription-based inhibitors of proinflammatory gene expression.