SNF4435C and D, novel nitrophenyl pyrones, have been isolated from the culture broth of an actinomycete strain SNF4435. The strain was identified as Streptomyces spectabilis from its morphological and cultural characteristics. SNF4435C and D showed a potent immunosuppressive activity in vitro and selectively suppressed B-cell proliferation induced by LPS versus T-cell proliferation induced by Con A.
SNF4435C and D are new immunosuppressants isolated from the culture broth of a strain of Streptomyces spectabilis. Their molecular formulas were determined as C28H31NO6 based on the HRFAB-MS analyses. The structures of SNF4435C and D were elucidated to be novel nitrophenyl pyrones having an intriguing tricyclic ring system and diastereoisomers of each other by spectroscopic analyses including various NMR measurements.
Streptomyces sp. WK-6326, a soil isolate, was found to produce an inhibitor of interleukin (IL)-4 signal transduction. Two structurally related compounds, a novel one designated deacetylravidomycin M and the known deacetylravidomycin, were isolated from the culture broth by solvent extraction, silica gel column chromatography and HPLC. Deacetylravidomycin M inhibited IL-4-induced CD23 expression in U937 cells without any cytotoxic effect, whereas deacetylravidomycin showed no inhibitory activity.
The structure of deacetylravidomycin M, an inhibitor of interleukin-4 signal transduction, was elucidated to be 6H-benzo[d]naphtho[l, 2-b]pyran-6-one, 4-[3, 6-dideoxy-3-(dimethylamino)-α-altropyranosyl]-l-hydroxy-10, 12-dimethoxy-8-methyl- by spectroscopic studies including NMR measurements.
Two novel butyrolactone antibiotics, cedarmycins A and B, were isolated from the cultured broth of the actinomycete Streptomyces sp. TP-A0456. The new compounds were purified by HP-20 resin, silica gel, ODS column chromatographies and preparative HPLC, consecutively. The structure of cedarmycin was determined by spectroscopic methods as an α, β-unsaturated butyrolactone with a fatty acid side chain. These compounds showed antibiotic activity against Gram-positive and -negative bacteria and yeasts. Among the tested organisms, cedarmycins potently inhibited the growth of Candida glabrata IFO 0622 with the MIC of 0.4, μg/ml, comparable to that of amphotericin B.
Bio-probes that inhibit the action of auxin are useful tools for the study of auxin signaling. To screen for specific inhibitors of auxin signaling, we used an Arabidopsis transgenic line harboring the auxin-inducible promoter derived from PS-IAA4/5 and the reporter gene, GUS (β-glucuronidase). In this transgenic plant, the exogenous auxin specifically enhanced the expression of the GUS reporter gene. A novel 22-membered spiroketal-macrolide, yokonolide A (1), and related previously known compound, A82548A (2), were isolated from Streptomyces diastatochromogenes B59 as inhibitors of auxin inducible gene expression. The absolute structure of 1 was determined by detailed spectral analyses and chemical derivatization. 1 and 2 completely inhibited the auxin-induced transcription of the reporter gene at 5 and 1 μM, respectively. In contrast, 1 and 2 did not affect the translation of GUS reporter transcripts. In addition, 1 and 2 did not inhibit the gibberellin-induced α-amylase expression at 100 μM in barley aleurone cells. These results suggest that 1 and 2 specifically inhibit auxin signaling leading to auxin-mediated gene expression.
To improve the efficiency of screening for anti-Microcystis compounds, we planned to use algae-lysing bacteria that kill the organisms of water blooms. A two step-screening process was carried out, i.e., the screening of algae-lysing bacteria and the selection of anti-Microcystis producers from the bacteria. Sources for the isolation of the bacteria were a co-cultivated fluid of a water sample with axenic Microcystis viridis, a water sample collected in a water bloom season, and a water bloom sample. The water bloom sample was the best source for the isolation of the algae-lysing bacteria and such bacteria were shown to exhibit potent activity. Seventeen strains out of 20 isolated algae-lysing bacteria produced anti-Microcystis activities, and one of the principles was the previously reported argimicin A. These results indicate that algae-lysing bacteria in water blooms may be good sources for potent and selective anticyanobacterial compounds.
A novel antifungal antibiotic, FR901469, was isolated from an unidentified fungus No. 11243. It is a water-soluble 40-membered macrocyclic lipopeptidolactone, consisting of D-Ala, L-Tyr, L-Val, trans-4OR-L-Pro, trans-3OH-L-Pro, threo-3OR-L-Gln, Gly, L-Orn, L-Thr, three residues of D-alloThr and a (3R)-hydroxypalmitic acid. Its structure, including absolute configurations, was unequivocally determined as 1 based on chemical and spectroscopic evidence.
Preparative-scale separation of colistin sulphate bulk sample was carried out on a preparative poly(styrene-divinylbenzene) stationary phase. Isocratic elution with acetonitrile - sodium sulphate solution (0.7% m/v; pH adjusted to 2.5 with TFA) - water (16:50:34, % v/v/v) was carried out at a flow rate of 4.0ml min-1. Six colistin components were isolated and characterized using 1H and 13C NMR. The molecular weights were confirmed by mass spectrometry. The structures of 2 components were determined for the first time. Polymyxin E7 was identified as having the same composition as polymyxin E1, except that the fatty acid moiety was 7-methyloctanoic acid. Isoleucine polymyxin E8 was characterized as having the same composition as isoleucine polymyxin E1 with 7-methylnonanoic acid as the fatty acid moiety.