TMC-86A, B and TMC-96, new proteasome inhibitors from Streptomyces sp. TC 1084 and Saccharothrix sp. TC 1094. I. Taxonomy, fermentation, isolation, and biological activities

TMC-86A, B and TMC-96, new 20S proteasome inhibitors with an epoxy-beta-aminoketone moiety, were isolated from the fermentation broth of Streptomyces sp. TC 1084 and Saccharothrix sp. TC 1094, respectively. TMC-86A, B and TMC-96 inhibited the chymotrypsin-like and peptidylglutamyl-peptide hydrolyzing activities of 20S proteasome with the following IC50 values: TMC-86A, 5.1 microM and 3.7microM; TMC-86B, 1.1 microM and 31 microM; TMC-96, 2.9 microM and 3.5 microM, respectively. TMC-86A, B and TMC-96 exhibited the weak inhibitory activity against the trypsin-like activity of 20S proteasome with IC50 values of 51 microM, 250 microM, and 36 microM, respectively. They did not inhibit m-calpain, cathepsin L, and trypsin at 100 microM, suggesting their high specificity for proteasome. Taxonomy of the producing strains is also described.     

Terreulactones A,B, C,and D: novel acetylcholinesterase inhibitors produced by Aspergillus terreus. I. Taxonomy,fermentation, isolation and biological activities

In the course of screening for selective inhibitors of acetylcholinesterase from the microbial metabolites, four new meroterpenoid compounds, terreulactones A, B, C and D were isolated from solid state fermentation of Aspergillus terreus Fb000501. They showed potent inhibitory activities against acetylcholinesterase with IC50 values in range of 0.06 to approximately 0.42 microM. In addition, they exhibited more than 500 to approximately 3000 times selectivity for acetylcholinesterase compared with butyrylcholinesterase.     

TMC-171A,B,C and TMC-154, novel polyketide antibiotics produced by Gliocladium sp. TC 1304 and TC 1282

Four new antibiotics, TMC-171A (2), B (3), C (4) and TMC-154 (5) have been isolated from the fermentation of fungal strains Gliocladium sp. TC 1304 and TC 1282, respectively. Spectroscopic and degradation studies have shown that TMC-171s and TMC-154 were new members of the TMC-151 class of antibiotics, unique polyketides modified with a D-mannose and a D-mannitol or a D-arabitol. These compounds showed moderate cytotoxicity to various tumor cell lines.     

Tyropeptins A and B, new proteasome inhibitors produced by Kitasatospora sp. MK993-dF2. I. Taxonomy, isolation, physico-chemical properties and biological activities

Tyropeptins A and B, new proteasome inhibitors, were isolated from the culture broth of Kitasatospora sp. MK993-dF2. They were purified using ethyl acetate extraction, silica gel column chromatography, Sephadex LH-20 column chromatography and HPLC. Tyropeptin A inhibited the chymotrypsin-like (ChT-L) and trypsin-like (T-L) activities of 20S proteasome with IC50 values of 0.1 microg/ml and 1.5 microg/ml respectively, but did not inhibit the peptidylglutamyl-peptide hydrolyzing (PGPH) activity of 20S proteasome at a concentration of 100 microg/ml. The inhibitory activities of tyropeptin A were about two times as strong as that of tyropeptin B. Taxonomy of the producing strain is also described.     

Eurystatins A and B, new prolyl endopeptidase inhibitors. I. Taxonomy, production, isolation and biological activities.

Eurystatins A and B, were isolated from the cultured broth of Streptomyces eurythermus R353-21. They showed specific and potent inhibitory activity against prolyl endopeptidase and did not show antimicrobial activity. No lethal toxicity was observed for the two compounds after ip administration in mice at 200 mg/kg.     

SNF4435C and D, novel immunosuppressants produced by a strain of Streptomyces spectabilis. I. Taxonomy, fermentation, isolation and biological activities

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.     

Tripropeptins, novel antimicrobial agents produced by Lysobacter sp. I. Taxonomy, isolation and biological activities

Peptide antibiotics tripropeptins A, B, C, D and Z were isolated from cultured cells and broth of Lysobacter sp. The differences among these components are in the lengths of the alkyl side chain. Tripropeptins are active against Gram-positive bacteria including MRSA in vitro. Bactericidal activity of tripropeptin C disappeared in the simultaneous presence of chloramphenicol, a bacteriostatic agent.     

Sakyomicins A, B, C and D: new quinone-type antibiotics produced by a strain of Nocardia. Taxonomy, production, isolation and biological properties

Actinomycete strain M-53, a new soil isolate, was found to produce four quinone-type antibiotics. Antibiotic sakyomicin components, A, B, C and D were isolated from the fermentation broth of strain M-53 by XAD-2 column chromatography, silica gel column chromatography and Sephadex LH-20 column chromatography. The components are active against Gram-positive bacteria. Strain M-53 was identified as a strain of genus Nocardia.     

TMC-69, a new antitumor antibiotic with Cdc25A inhibitory activity, produced by Chrysosporium sp. TC1068. Taxonomy, fermentation and biological activities

A new antibiotic designated TMC-69 has been isolated from the fermentation broth of a fungal strain Chrysosporium sp. TC 1068. TMC-69 exhibited moderate in vitro cytotoxic activity. TMC-69-6H, a derivative of TMC-69 prepared by hydrogenation, possessed more potent in vitro cytotoxicity than TMC-69, and exhibited in vivo antitumor activity against murine P388 leukemia and B16 melanoma. TMC-69-6H was found to specifically inhibit Cdc25A and B phosphatases.     

Bisabosquals, novel squalene synthase inhibitors. I. Taxonomy, fermentation, isolation and biological activities

In the course of screening for yeast squalene synthase inhibitors, bisabosqual A was isolated from the culture broth of Stachybotrys sp. RF-7260. The related compounds bisabosquals B, C and D were also isolated from Stachybotrys ruwenzoriensis RF-6853. Bisabosquals inhibited squalene synthases. IC50 values of bisabosqual A against the microsomal squalene synthases from Saccharomyces cerevisiae, Candida albicans, HepG2 cell and rat liver were 0.43, 0.25, 0.95 and 2.5 microg/ml, respectively. Bisabosqual C exhibited inhibitory activities similar to bisabosqual A. Bisabosqual A showed broad spectrum antifungal activity in vitro.     

Melanocins A, B and C, new melanin synthesis inhibitors produced by Eupenicillium shearii. I. Taxonomy, fermentation, isolation and biological properties

New melanin synthesis inhibitors, melanocins A, B and C, were isolated from the fermentation broth and mycelium extract of Eupenicillium shearii F80695. Melanocin A, an isocyanide compound, inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with IC50 value of 9.0 nM and MIC value of 0.9 microM, respectively. Melanocin A also inhibited growth of Streptomyces bikiniensis. While, the structurally very related but non-isocyanide compounds melanocins B and C did not show inhibitory activity in these assays. Melanocins A, B and C showed potent antioxidant activity with scavenging activity of DPPH radical and superoxide anion radical.     

SW-163C and E, novel antitumor depsipeptides produced by Streptomyces sp. I. Taxonomy, fermentation, isolation and biological activities

Novel depsipeptides, SW-163C and E were isolated from the culture broth of an actinomycete strain. The producing organism, designated as SNA15896, was identified as a member of Streptomyces from its morphological and cultural characteristics. SW-163C and E exhibited potent antitumor activities against various tumor cell lines in vitro and against murine leukemia P388 in vivo. The compounds also showed antimicrobial activities.     

SIIA-C2191-A和B,黄灰链霉菌产生的多环(口山)酮类新抗生素Ⅰ.菌种分类,发酵,分离纯化和生物学活性

在筛选具有生物活性的放线菌新代谢产物的过程中,从放线菌SIIA-A021 91的发酵产物中发现了新的多环(口山)酮类抗生素SIIA-C2191A及其溴代类似物SIIA-C2191B.基于形态学、化学分类和16SrDNA等数据,将分离自渤海湾沙地土壤的产生菌鉴定为灰黄链霉菌.活性化合物采用减压快速层析法和制备型高效液相进行分离纯化.化合物SIIA-C2191A和SIIA-C2l9B均对革兰氏阳性菌显示强抗菌活性,但对革兰氏阴性菌的抗菌活性较弱.     

Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. I. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Benastatins have been isolated as part of a program designed to find microorganism-produced inhibitors of glutathione S-transferase from Streptomyces sp. MI384-DF12. They were purified by chromatography of reversed-phase silica gel, silica gel and Capcell Pak C18 (HPLC) followed by solvent extraction and then isolated as yellow powders. Benastatins A and B have the molecular formulae, C30H28O7 and C30H30O7, respectively. They were competitive with 3,4-dichloronitrobenzene as the substrate, and the inhibition constants (Ki) of benastatins A and B were 5.0 x 10(-6) and 3.7 x 10(-6), respectively.     

Janthinocins A, B and C, novel peptide lactone antibiotics produced by Janthinobacterium lividum. I. Taxonomy, fermentation, isolation, physico-chemical and biological characterization

Janthinocins A, B and C are novel antibacterial agents produced by Janthinobacterium lividum. They were isolated from fermentation broths and characterized by UV, IR, NMR and mass spectroscopy. They are cyclic decapeptide lactones with marked activity against aerobic and anaerobic Gram-positive bacteria and are 2 to 4 times more potent in vitro than vancomycin. Janthinocins A and B were also found to be effective in a Staphylococcus aureus systemic infection in mice.     

Dactylocyclines, novel tetracycline derivatives produced by a Dactylosporangium sp. I. Taxonomy, production, isolation and biological activity.

A screen for antibiotics with activity against tetracycline-resistant microorganisms has led to the isolation of Dactylosporangium sp. (ATCC 53693), a producer of several novel tetracycline derivatives. The major fermentation products, dactylocyclines A and B, were purified and MIC values determined against tetracycline-resistant and tetracycline-sensitive Gram-positive bacteria. The dactylocyclines represent the first naturally occurring tetracycline C2 amides which lack cross resistance with tetracycline.     

Radamycin,a novel thiopeptide produced by streptomyces sp. RSP9. I. Taxonomy,fermentation, isolation and biological activities

The newly isolated strain Streptomyces sp. RSP9 produces two thiopeptides; one of them is methylsulfomycin I, which shows potent antibiotic activity against several gram-positive bacteria such as Micrococcus luteus and Staphylococcus aureus. The other is a new thiopeptide named radamycin. In the present work, this compound was purified and tested against several microorganisms and no antibiotic activity was detected in the assays. However, it does have a very strong capacity as an inducer of the tipA promoter, and indeed is the first reported molecule with tipA promoter induction capacity without detectable antibiotic activity. Induction of the tipA promoter also occurs with methylsulfomycin I.