Beauveria sp. FO-6979, a soil isolate, was found to produce inhibitors of lipid droplet formation in mouse peritoneal macrophages. A new compound beauveriolide III was isolated along with a known compound beauveriolide I from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography, silica gel column chromatography and preparative HPLC. Beauveriolides I and III caused a reduction in the number and size of cytosolic lipid droplets in macrophages at 10 μM without any cy to toxic effect on macrophages.
The structure of fungal beauveriolide III, an inhibitor of lipid droplet formation in mouse macrophages, was elucidated to be cyclo-[(3S, 4S)-3-hydroxy-4-methyloctanoyl-Lphenylalanyl-L-alanyl-D-allo-isoleucyl] by spectral analyses and chemical degradation.
A novel tricyclic diterpenoid antibiotic, brasilicardin A, was isolated from the culture broth of Nocardia brasiliensis IFM 0406. The antibiotic exhibited immunosuppressive activity in a mouse mixed lymphocyte reaction (MLR) assay system and its IC50 value was 0.057 μg/ml. Although the inhibitory activity of cyclosporin A (CyA) against IL-2 production was confirmed in the MLR assay system, brasilicardin A did not have the activity. The results of in vitro toxicity testing of brasilicardin A against various human cell lines were compared with those of CyA.
IC202A, a new immunosuppressive compound, was isolated from the culture filtrate of Streptoalloteichus sp. 1454-19. It showed a suppressive effect on mixed lymphocyte culture reaction with an IC50 value of 3.6 μg/ml and mitogen induced lymphocyte blastogenesis in vitro.
IC202A (1) was isolated from the culture filtrate of Streptoalloteichus sp. 1454-19. The structure of 1 was determined by spectral analysis including a variety of twodimentional NMR and FAB-MS experiments. IC202A is a ferrioxamine-related compound containing a butylidene N-oxide function.
A new antibiotic termed zelkovamycin was isolated from the fermentation broth of Streptomyces sp. K96-0670 by solvent extraction, ODS column chromatography and preparative HPLC. Zelkovamycin showed antibacterial activity against Xanthomonas oryzae, Acholeplasma laidlawii, Pyricularia oryzae and Staphylococcus aureus.
The structure of antibiotic zelkovamycin was elucidated as a cyclic pep tide comprising glycyl, 2-aminobutanoyl, 2-ammo-2-butenoyl, N-methyl glycyl, alanyl, 1, 3-thiazoyl, 7-methoxytryptophanyl and 2-methyldehydrothreonyl residues. The sequence of the amino acids was established by spectroscopic studies including 1H-1H COSY, 13C-1H COSY, 13C-1H HMQC, 13C-1H HMBC, 15N-1H HMQC and 15N-1H HMBC NMR experiments.
The growth and production kinetics of a teicoplanin producing strain of Actinoplanes teichomyceticus (ATCC 31121) was investigated during batch cultivations on defined media. The growth was characterised by two exponential growth phases (EGPs), with a higher specific growth rate in the first than in the second phase. Also the specific rate of formation of teicoplanin was significantly lower in the second phase than in the first phase. This two-phased growth pattern was suggested to be caused by inhibition of growth by teicoplanin accumulated. Furthermore high concentrations of ammonia or phosphate reduced both the specific growth rate in the first EGP and the total production of teicoplanin.
Deoxyspergualin (DSG) has both antitumor and immunosuppressive activities. We explored the mechanism of DSG activities using an aqueous soluble analogue, methyldeoxyspergualin (MeDSG) for in vitro culture studies. It is known that DSG has inhibitory effects on cell proliferation, and we also observed that MeDSG inhibited [3H]-thymidine incorporation by rapidly dividing murine T cell hybridomas. However, when tetrazolium (MTT) colorimetric assay was adopted to evaluate its inhibitory effects on cell proliferation, MeDSG induced an enhanced MTT reduction. When we examined whether these results were applicable to the actively dividing cells of other origins than T cells, similar effects were seen with Raji cells, J774.1 cells and NIH3T3 cells. N-30, another analogue which was capable of suppressing anti-SRBC antibody production in vivo, also induced inhibition of cell growth and an enhanced MTT reduction. In contrast, the analogue which failed to prevent the antibody production, neither enhanced MTT reduction nor inhibited cell proliferation. Our results demonstrated that the ability to generate MTT formazan in dividing cells is a common property among DSG analogue with the immunosuppressive and antiproliferative activities.
A systematic analysis of the bacteriostatic/bactericidal effect of several antibiotics used in veterinary medicine was carried out by time-kill kinetic analysis using P. haemolytica, P. multocida, A. pleuropneumoniae, and E. coli. The antibiotics tested were enrofloxacin, danofloxacin, erythromycin, tilmicosin, penicillin G, ceftiofur and tetracycline. Unexpectedly, the antibiotics well characterized as bacteriostatic agents against human pathogens such as tetracycline and macrolides, showed bactericidal activity against P. haemolytica and A. pleuropneumoniae. In contrast, tetracycline and erythromycin were bacteriostatic and tilmicosin was bactericidal against P. multocida. In addition, P. multocida was killed by fluoroquinolones at a slower rate than the other bacteria. Spectrum analysis revealed that ceftiofur and tilmicosin were good substrates of the universal efflux pump, AcrA/B, but penicillin and tetracycline were not. The fluoroquinolones were modest substrates for AcrA/B.