A series of diterpenes were isolated from the fermentation broth of a fungus, Oidiodendron griseum CL37215. The diterpenes were identified as LL-Z1271α, LL-Z1271γ, CJ-14, 445, PR 1388, CJ-14, 604 and a new diterpene, CJ-14, 515. They inhibited both lipopolysaccharide-induced interleukin-1β and tumor necrosis factor-α production in human whole blood with IC50s of the range from 0.049 to 100 μM.
New cytokine production inhibitors, CJ-14, 877 (I) and CJ-14, 897 (II), were isolated from the fermentation broth of a basidiomycete, Marasmiellus sp. CL21624. Their structures were determined to be methyl-(7R, 8S)-5-(7, 8-dihydroxypropyl)pyridine-2-carboxylate and methyl(7R, 8S)-5-(8-acetoxy-7-hydroxypropyl)pyridme-2-carboxylate, respectively, by spectroscopic analyses. These compounds showed inhibitory activities for lipopolysaccharide-induced production of interleukin-1β and tumor necrosis factor-a in human whole blood with IC50 values of the range from 0.059 to 2.6 JUM.
A new apoptosis inducer, ammocidin, was isolated from the culture broth of Saccharothnx sp. AJ9571. Ammocidin induced apoptotic cell death in Ras-dependent Ba/F3-V12 cells with an IC50 of 66ng/ml. No cell death was observed in IL-3-dependent Ba/F3-V12 cells at less than 100μg/ml of ammocidin. Ammocidin significantly reduced the phosphorylation level of MAPK and S6K that mediate the anti-apoptotic function of Ras.
The structure of ammocidin, a new apoptosis inducer in Ras-dependent cells from Saccharothnx sp. AJ9571, was elucidated to be as shown in Fig. 1 by NMR and degradation studies. Ammocidin consists of a 20-membered macrolide ring and three deoxy sugars identified as 6-deoxy-L-glucose, D-digitoxose and D-olivomycose.
The new pluramycin-type antibiotics pluraflavin A, C43H54N2O14, pluraflavin B, C43H56N2O15, and pluraflavin E, C36H41NO14 were isolated from cultures of the Saccharothrix species DSM 12931. The structures of the novel compounds were elucidated with the aid of 2D NMR and mass spectrometric investigations. The characteristic structural element of pluraflavins A and B is an additional 4-epi-vancosamine unit at position 13 of the anthraquinone-γ-pyrone ring system. Pluraflavin E has a carboxyl group in this position. Pluraflavin A has a reactive dimethyl epoxide side chain at position 2 of the anthraquinone-γ-pyrone aglycon, which may explain the high activity of the antibiotic. The outstanding biological characteristic of pluraflavin A is its powerful, organ-dependent cytostatic action: the IC50 in the colon carcinoma proliferation assay is in the subnanomolar range.
Two novel secondary metabolites, bagremycin A (2) and B (3), were detected in the culture filtrate of Streptomyces sp. Tü 4128 by HPLC-diode-array screening. They are phenol esters of 3-amino-4-hydroxybenzoic acid with a derivative of p-coumaric acid and show a moderate activity against Gram-positive bacteria and some fungi.
2-Deoxy-D-glucose-6-phosphate ketol-isomerase (EC 184.108.40.206) forms glucosamine-6-phosphate and glutamate from fructose-6-phosphate and glutamine and plays an important role in chitin synthesis in fungi. We have established a new assay for fungal ketol-isomerase activity that is amenable to high throughput screening to identify enzyme inhibitors. Aspergillus fumigatus crude lysate was incubated with substrates and after incubation, reactions were terminated. Glutamate dehydrogenase, nitro blue tetrazolium chloride, phenazine methosulfate and β-NAD were added and the amount of glutamate formed by ketol-isomerase activity was determined by measuring OD585nm. A feedback inhibitor, UDP-N-acetylglucosamine, of fungal ketol-isomerase was successfully detected by this assay (IC50-0.48 mM). In a pilot scale screening, an active extract from an extremophilic bacterium was found, and the extract showed antifungal activity against A. fumigatus, Candida albicans and C glabrata.